This entry represents the RNA recognition motif 1 (RRM1) of polypyrimidine tract-binding protein 1 (PTBP1). PTBP1 (also known as PTB) is involved in numerous post-transcriptional steps in gene expression in both the nucleus and cytoplasm. It can act as a negative regulator of alternative splicing and as an activator of translation driven by IRESs (internal ribosome entry segments) []. It contains four RNA recognition motifs (RRM). RRM1 and RRM2 are independent from each other and separated by flexible linkers. By contrast, there is an unusual and conserved interdomain interaction between RRM3 and RRM4. It is widely held that only RRMs 3 and 4 are involved in RNA binding and RRM2 mediates PTB homodimer formation. However, new evidence shows that the RRMs 1 and 2 also contribute substantially to RNA binding. Moreover, PTB may not always dimerize to repress splicing. It is a monomer in solution [, ].
This entry represents the RNA recognition motif 1 (RRM1) of RBM40 (also known as U11/U12-65K). RBM40 serves as a bridging factor between the U11 and U12 snRNPs []. It contains two repeats of an RNA recognition motif (RRM), connected by a linker that includes a proline-rich region. It binds to the U11-associated 59K protein via its RRM1 and employs the RRM2 to bind hairpin III of the U12 small nuclear RNA (snRNA). The proline-rich region might be involved in protein-protein interactions [].
RNPC3 serves as a bridging factor between the U11 and U12 snRNPs. It contains two RNA recognition motifs (RRMs), connected by a linker that includes a proline-rich region. It binds to the U11-associated 59K protein via its RRM1 and employs the RRM2 to bind hairpin III of the U12 small nuclear RNA (snRNA). The proline-rich region might be involved in protein-protein interactions [, ]. RBM41 contains only one RRM. Its biological function remains unclear.
This entry represents the RNA recognition motif 1 (RRM1) of CELF-3, CELF-4, CELF-5, CELF-6, all of which belong to the CUGBP1 and ETR-3-like factors (CELF) or BRUNOL (Bruno-like) family of RNA-binding proteins [, ]. The CELF family members have three RRMs []. It has been shown that either RRM1 or RRM2 of CELF-4 are necessary and sufficient for muscle-specific splicing enhancer (MSE) RNA binding []. The human CELF family has six members, which can be divided into two subfamilies based on their phylogeny: CELF1-2 and CELF3-6. They all possess alternative splicing activity in the nucleus and all have cytoplasmic roles, including regulating mRNA adenylation status, stability, and translation in various cell types [].
This entry represents the RNA recognition motif 3 (RRM3) of HuB. HuB (also known as ELAV-like protein 2 or Hel-N1) is one of the neuronal members of the Hu family []. The neuronal Hu proteins play important roles in neuronal differentiation, plasticity and memory. HuB is also expressed in gonads. It is up-regulated during neuronal differentiation of embryonic carcinoma P19 cells []. Like other Hu proteins, HuB contains three RNA recognition motifs (RRMs). RRM1 and RRM2 may cooperate in binding to an AU-rich RNA element (ARE). RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions [].
This entry represents the RNA recognition motif 3 (RRM3) of HuC (also known as ELAV-like protein 3), one of the neuronal members of the Hu family. The neuronal Hu proteins play important roles in neuronal differentiation, plasticity and memory []. Like other Hu proteins, HuC contains three RNA recognition motifs (RRMs). RRM1 and RRM2 may cooperate in binding to an AU-rich RNA element (ARE) []. The AU-rich element binding of HuC can be inhibited by flavonoids. RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions [].
This entry represents the RNA recognition motif 2 (RRM2) of HuB. HuB (also known as ELAV-like protein 2 or Hel-N1) is one of the neuronal members of the Hu family []. The neuronal Hu proteins play important roles in neuronal differentiation, plasticity and memory. HuB is also expressed in gonads. It is up-regulated during neuronal differentiation of embryonic carcinoma P19 cells []. Like other Hu proteins, HuB contains three RNA recognition motifs (RRMs). RRM1 and RRM2 may cooperate in binding to an AU-rich RNA element (ARE). RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions [].
This entry represents the RNA recognition motif 1 (RRM1) of nucleolysin TIAR (TIA-1-related protein). TIAR is a cytotoxic granule-associated RNA-binding protein that shows high sequence similarity with TIA-1 []. TIAR plays a critical role in transcriptional and posttranscriptional regulation of gene expression []. It binds to target mRNA and DNA via its RNA recognition motif (RRM) domains and is involved in both splicing regulation and translational repression via the formation of stress granules []. TIAR is composed of three N-terminal highly homologous RNA recognition motifs (RRMs) and a glutamine-rich C-terminal auxiliary domain containing a lysosome-targeting motif. Its RRMs are involved in binding to U-rich RNA, but with unequal contributions. RRM2 of TIAR is the major RNA- and DNA-binding domain [].
This entry represents the RNA recognition motif 2 (RRM2) of nucleolysin TIAR (TIA-1-related protein).TIAR is a cytotoxic granule-associated RNA-binding protein that shows high sequence similarity with TIA-1 []. TIAR plays a critical role in transcriptional and posttranscriptional regulation of gene expression []. It binds to target mRNA and DNA via its RNA recognition motif (RRM) domains and is involved in both splicing regulation and translational repression via the formation of stress granules []. TIAR is composed of three N-terminal highly homologous RNA recognition motifs (RRMs) and a glutamine-rich C-terminal auxiliary domain containing a lysosome-targeting motif. Its RRMs are involved in binding to U-rich RNA, but with unequal contributions. RRM2 of TIAR is the major RNA- and DNA-binding domain [].
This entry represents the RNA recognition motif 3 (RRM3) of nucleolysin TIAR (TIA-1-related protein).TIAR is a cytotoxic granule-associated RNA-binding protein that shows high sequence similarity with TIA-1 []. TIAR plays a critical role in transcriptional and posttranscriptional regulation of gene expression []. It binds to target mRNA and DNA via its RNA recognition motif (RRM) domains and is involved in both splicing regulation and translational repression via the formation of stress granules []. TIAR is composed of three N-terminal highly homologous RNA recognition motifs (RRMs) and a glutamine-rich C-terminal auxiliary domain containing a lysosome-targeting motif. Its RRMs are involved in binding to U-rich RNA, but with unequal contributions. RRM2 of TIAR is the major RNA- and DNA-binding domain [].
This entry represents the RNA recognition motif 3 (RRM3) of HuD (also known as ELAV-like protein 4), one of the neuronal members of the Hu family. The neuronal Hu proteins play important roles in neuronal differentiation, plasticity and memory. HuD has been implicated in various aspects of neuronal function, such as the commitment and differentiation of neuronal precursors as well as synaptic remodeling in mature neurons []. HuD also functions as an important regulator of mRNA expression in neurons by interacting with AU-rich RNA element (ARE) and stabilizing multiple transcripts []. Moreover, HuD regulates the nuclear processing/stability of N-myc pre-mRNA in neuroblastoma cells []. Like other Hu proteins, HuD contains three RNA recognition motifs (RRMs). RRM1 and RRM2 may cooperate in binding to an ARE. RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions [].
This entry represents the RNA recognition motif 2 (RRM2) of HuR, also known as ELAV-like protein 1 (ELAV-1), the ubiquitously expressed Hu family member [, ]. HuR binds to AU-rich RNA element (ARE) in target mRNAs and stabilizes them against degradation. It also regulates the nuclear import of proteins []. It has a variety of biological functions mostly related to the regulation of cellular response to DNA damage and other types of stress. HuR has an anti-apoptotic function during early cell stress response []. HuR may be important in muscle differentiation, adipogenesis, suppression of inflammatory response and modulation of gene expression in response to chronic ethanol exposure and amino acid starvation [].Like other Hu proteins, HuR contains three RNA recognition motifs (RRMs). RRM1 and RRM2 may cooperate in binding to an AU-rich RNA element (ARE). RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions [].
The human CELF family has six members, which can be divided into two subfamilies based on their phylogeny: CELF1-2 and CELF3-6. This entry represents the RNA recognition motif 2 (RRM2) of CELF-1 and CELF-2 protein. CELF-1 and CELF-2 belong to the CELF (CUGBP and ETR-3 Like Factor)/Bruno-like protein family, whose members play important roles in the regulation of alternative splicing and translation. CELF-1 and CELF-2 share sequence similarity to the Drosophila Bruno protein and binds to the Bruno response elements (cis-acting sequences in the 3'-untranslated region (UTR) ofoskar mRNA) [].The human CELF-1 (also known as CUG-BP or BRUNOL-2) binds to RNA substrates and recruits PARN deadenylase []. It preferentially targets UGU-rich mRNA elements []. CELF-1 has been implicated in onset of type 1 myotonic dystrophy (DM1), a neuromuscular disease associated with an unstable CUG triplet expansion in the 3'-UTR (3'-untranslated region) of the DMPK (myotonic dystrophy protein kinase) gene [, ]. CELF-1 contain three highly conserved RNA recognition motifs (RRMs): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C terminus of the protein. The Xenopus homologue of CELF-1 is EDEN-BP (embryo deadenylation element-binding protein), which mediates sequence-specific deadenylation of Eg5 mRNA. It binds specifically to the EDEN motif in the 3'-untranslated regions of maternal mRNAs and targets these mRNAs for deadenylation and translational repression []. The two N-terminal RRMs of EDEN-BP are necessary for the interaction with EDEN as well as a part of the linker region (between RRM2 and RRM3). Oligomerization of EDEN-BP is required for specific mRNA deadenylation and binding []. CELF-2 (also known as CUGBP2 or ETR-3) shares high sequence identity with CELF-1, but shows different binding specificity; it binds preferentially to sequences with UG repeats and UGUU motifs. It also binds to the 3'-UTR of cyclooxygenase-2 messages, affecting both translation and mRNA stability, and binds to apoB mRNA, regulating its C to U editing []. CELF-2 also contains three highly conserved RRMs. It binds to RNA via the first two RRMs, which are also important for localization in the cytoplasm. The splicing activation or repression activity of CELF-2 on some specific substrates is mediated by RRM1/RRM2. Both, RRM1 and RRM2 of CELF-2, can activate cardiac troponin T (cTNT) exon 5 inclusion. In addition, CELF-2 possesses a typical arginine and lysine-rich nuclear localization signal (NLS) in the C terminus, within RRM3 [].
The human CELF family has six members, which can be divided into two subfamilies based on their phylogeny: CELF1-2 and CELF3-6. This entry represents the RNA recognition motif 3 (RRM3) of CELF-1 andCELF-2 protein. CELF-1 and CELF-2 belong to the CELF (CUGBP and ETR-3 Like Factor)/Bruno-like protein family, whose members play important roles in the regulation of alternative splicing and translation. CELF-1 and CELF-2 share sequence similarity to the Drosophila Bruno protein and binds to the Bruno response elements (cis-acting sequences in the 3'-untranslated region (UTR) ofoskar mRNA) [].The human CELF-1 (also known as CUG-BP or BRUNOL-2) binds to RNA substrates and recruits PARN deadenylase []. It preferentially targets UGU-rich mRNA elements []. CELF-1 has been implicated in onset of type 1 myotonic dystrophy (DM1), a neuromuscular disease associated with an unstable CUG triplet expansion in the 3'-UTR (3'-untranslated region) of the DMPK (myotonic dystrophy protein kinase) gene [, ]. CELF-1 contain three highly conserved RNA recognition motifs (RRMs): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C terminus of the protein. The Xenopus homologue of CELF-1 is EDEN-BP (embryo deadenylation element-binding protein), which mediates sequence-specific deadenylation of Eg5 mRNA. It binds specifically to the EDEN motif in the 3'-untranslated regions of maternal mRNAs and targets these mRNAs for deadenylation and translational repression []. The two N-terminal RRMs of EDEN-BP are necessary for the interaction with EDEN as well as a part of the linker region (between RRM2 and RRM3). Oligomerization of EDEN-BP is required for specific mRNA deadenylation and binding []. CELF-2 (also known as CUGBP2 or ETR-3) shares high sequenceidentity with CELF-1, but shows different binding specificity; it binds preferentially to sequences with UG repeats and UGUU motifs. It also binds to the 3'-UTR of cyclooxygenase-2 messages, affecting both translation and mRNA stability, and binds to apoB mRNA, regulating its C to U editing []. CELF-2 also contains three highly conserved RRMs. It binds to RNA via the first two RRMs, which are also important for localization in the cytoplasm. The splicing activation or repression activity of CELF-2 on some specific substrates is mediated by RRM1/RRM2. Both, RRM1 and RRM2 of CELF-2, can activate cardiac troponin T (cTNT) exon 5 inclusion. In addition, CELF-2 possesses a typical arginine and lysine-rich nuclear localization signal (NLS) in the C terminus, within RRM3 [].
This entry represents the RNA recognition motif 1 (RRM1) of yeast protein Pub1.Pub1 (poly(U)-binding protein) is a yeast homologue of the mammalian ELAV-like proteins HuR and TIA-1/TIAR. Pub1 regulates cellular mRNA decay, and it also regulates gene expression by diverse posttranscriptional mechanisms []. It has been identified as both a heterogeneous nuclear RNA-binding protein (hnRNP) and a cytoplasmic mRNA-binding protein (mRNP), which may be stably bound to a translationally inactive subpopulation of mRNAs within the cytoplasm []. It is distributed in both, the nucleus and the cytoplasm, and binds to poly(A)+ RNA (mRNA or pre-mRNA). Although it is one of the major cellular proteins cross-linked by UV light to polyadenylated RNAs in vivo, Pub1 is nonessential for cell growth in yeast []. Pub1 also binds to T-rich single stranded DNA (ssDNA) []; however, there is no strong evidence implicating Pub1 in the mechanism of DNA replication. Pub1 contains three RNA recognition motifs (RRMs) and a GAR motif (glycine and arginine rich stretch) that is located between RRM2 and RRM3.
This entry represents the RNA recognition motif 3 (RRM3) of yeast protein Pub1.Pub1 (poly(U)-binding protein) is a yeast homologue of the mammalian ELAV-like proteins HuR and TIA-1/TIAR. Pub1 regulates cellular mRNA decay, and it also regulates gene expression by diverse posttranscriptional mechanisms []. It has been identified as both a heterogeneous nuclear RNA-binding protein (hnRNP) and a cytoplasmic mRNA-binding protein (mRNP), which may be stably bound to a translationally inactive subpopulation of mRNAs within the cytoplasm []. It is distributed in both, the nucleus and the cytoplasm, and binds to poly(A)+ RNA (mRNA or pre-mRNA). Although it is one of the major cellular proteins cross-linked by UV light to polyadenylated RNAs in vivo, Pub1 is nonessential for cell growth in yeast []. Pub1 also binds to T-rich single stranded DNA (ssDNA) []; however, there is no strong evidence implicating Pub1 in the mechanism of DNA replication. Pub1 contains three RNA recognition motifs (RRMs) and a GAR motif (glycine and arginine rich stretch) that is located between RRM2 and RRM3.
This entry represents the RNA recognition motif 3 (RRM3) of heterogeneous nuclear ribonucleoprotein H3 (hnRNP H3). hnRNP H3 (also termed hnRNP 2H9) is a nuclear RNA binding protein that belongs to the hnRNP H protein family that also includes hnRNP H, hnRNP H2, and hnRNP F. This family is involved in mRNA processing and exhibit extensive sequence homology. Little is known about the functions of hnRNP H3 except for its role in the splicing arrest induced by heat shock [, ]. The typical hnRNP H proteins contain contain three RNA recognition motifs (RRMs), except for hnRNP H3, in which the RRM1 is absent. RRM1 and RRM2 are responsible for the binding to the RNA at DGGGD motifs, and they play an important role in efficiently silencing the exon. Members in this family can regulate the alternative splicing of the fibroblast growth factor receptor 2 (FGFR2) transcripts, and function as silencers of FGFR2 exon IIIc through an interaction with the exonic GGG motifs. The lack of RRM1 could account for the reduced silencing activity within hnRNP H3. In addition, like other hnRNP H protein family members, hnRNP H3 has an extensive glycine-rich region near the C terminus, which may allow it to homo- or heterodimerize [].
This entry represents the RNA recognition motif 2 (RRM2) of heterogeneous nuclear ribonucleoprotein H3 (hnRNP H3).hnRNP H3 (also termed hnRNP 2H9) is a nuclear RNA binding protein that belongs to the hnRNP H protein family that also includes hnRNP H, hnRNP H2, and hnRNP F. This family is involved in mRNA processing and exhibit extensive sequence homology. Little is known about the functions of hnRNP H3 except for its role in the splicing arrest induced by heat shock [, ]. The typical hnRNP H proteins contain contain three RNA recognition motifs (RRMs), except for hnRNP H3, in which the RRM1 is absent. RRM1 and RRM2 are responsible for the binding to the RNA at DGGGD motifs, and they play an important role in efficiently silencing the exon. Members in this family can regulate the alternative splicing of the fibroblast growth factor receptor 2 (FGFR2) transcripts, and function as silencers of FGFR2 exon IIIc through an interaction with the exonic GGG motifs. The lack of RRM1 could account for the reduced silencing activity within hnRNP H3. In addition, like other hnRNP H protein family members, hnRNP H3 has an extensive glycine-rich region near the C terminus, which may allow it to homo- or heterodimerize [].
This entry represents the RNA recognition motif 3 (RRM3) of TIA-1.TIA-1 is the 40kDa isoform of T-cell-restricted intracellular antigen-1 (TIA-1, also known as Cytotoxic granule associated RNA binding protein TIA1), a cytotoxic granule-associated RNA-binding protein mainly found in the granules of cytotoxic lymphocytes [, ]. TIA-1 regulate alternative pre-mRNA splicing by promoting the use of suboptimal 5' splice sites followed by uridine-rich intronic enhancer sequences. It can be phosphorylated by a serine/threonine kinase that is activated during Fas-mediated apoptosis, and functions as the granule component responsible for inducing apoptosis in cytolytic lymphocyte (CTL) targets []. Under conditions of rapid oxygen decline and extreme hypoxia, TIA-1 can aggregate with TIAR and suppress the HIF-1alpha pathway []. TIA-1 binds Zn, which is involved in formation and recruitment to stress granules [].TIA-1 is composed of three N-terminal highly homologous RNA recognition motifs (RRMs) and a glutamine-rich C-terminal auxiliary domain containing a lysosome-targeting motif. It interacts with RNAs containing short stretches of uridylates and its RRM2 can mediate the specific binding to uridylate-rich RNAs [].
This entry represents the RNA recognition motif 2 (RRM2) of TIA-1.TIA-1 is the 40kDa isoform of T-cell-restricted intracellular antigen-1 (TIA-1, also known as Cytotoxic granule associated RNA binding protein TIA1), a cytotoxic granule-associated RNA-binding protein mainly found in the granules of cytotoxic lymphocytes [, ]. TIA-1 regulate alternative pre-mRNA splicing by promoting the use of suboptimal 5' splice sites followed by uridine-rich intronic enhancer sequences. It can be phosphorylated by a serine/threonine kinase that is activated during Fas-mediated apoptosis, and functions as the granule component responsible for inducing apoptosis in cytolytic lymphocyte (CTL) targets []. Under conditions of rapid oxygen decline and extreme hypoxia, TIA-1 can aggregate with TIAR and suppress the HIF-1alpha pathway []. TIA-1 binds Zn, which is involved in formation and recruitment to stress granules [].TIA-1 is composed of three N-terminal highly homologous RNA recognition motifs (RRMs) and a glutamine-rich C-terminal auxiliary domain containing a lysosome-targeting motif. It interacts with RNAs containing short stretches of uridylates and its RRM2 can mediate the specific binding to uridylate-rich RNAs [].
This entry represents the RNA recognition motif 1 (RRM1) of TIA-1.TIA-1 is the 40kDa isoform of T-cell-restricted intracellular antigen-1 (TIA-1, also known as Cytotoxic granule associated RNA binding protein TIA1), a cytotoxic granule-associated RNA-binding protein mainly found in the granules of cytotoxic lymphocytes [, ]. TIA-1 regulate alternative pre-mRNA splicing by promoting the use of suboptimal 5' splice sites followed by uridine-rich intronic enhancer sequences. It can be phosphorylated by a serine/threonine kinase that is activated during Fas-mediated apoptosis, and functions as the granule component responsible for inducing apoptosis in cytolytic lymphocyte (CTL) targets []. Under conditions of rapid oxygen decline and extreme hypoxia, TIA-1 can aggregate with TIAR and suppress the HIF-1alpha pathway []. TIA-1 binds Zn, which is involved in formation and recruitment to stress granules [].TIA-1 is composed of three N-terminal highly homologous RNA recognition motifs (RRMs) and a glutamine-rich C-terminal auxiliary domain containing a lysosome-targeting motif. It interacts with RNAs containing short stretches of uridylates and its RRM2 can mediate the specific binding to uridylate-rich RNAs [].
The human CELF family has six members, which can be divided into two subfamilies based on their phylogeny: CELF1-2 and CELF3-6. This entry represents the RNA recognition motif 1 (RRM1) of CELF-1 and CELF-2 protein. CELF-1 and CELF-2 belong to the CELF (CUGBP and ETR-3 Like Factor)/Bruno-like protein family, whose members play important roles in the regulation of alternative splicing and translation. CELF-1 and CELF-2 share sequence similarity to the Drosophila Bruno protein and binds to the Bruno response elements (cis-acting sequences in the 3'-untranslated region (UTR) ofoskar mRNA) [].The human CELF-1 (also known as CUG-BP or BRUNOL-2) binds to RNA substrates and recruits PARN deadenylase []. It preferentially targets UGU-rich mRNA elements []. CELF-1 has been implicated in onset of type 1 myotonic dystrophy (DM1), a neuromuscular disease associated with an unstable CUG triplet expansion in the 3'-UTR (3'-untranslated region) of the DMPK (myotonic dystrophy protein kinase) gene [, ]. CELF-1 contain three highly conserved RNA recognition motifs (RRMs): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C terminus of the protein. The Xenopus homologue of CELF-1 is EDEN-BP (embryo deadenylation element-binding protein), which mediates sequence-specific deadenylation of Eg5 mRNA. It binds specifically to the EDEN motif in the 3'-untranslated regions of maternal mRNAs and targets these mRNAs for deadenylation and translational repression []. The two N-terminal RRMs of EDEN-BP are necessary for the interaction with EDEN as well as a part of the linker region (between RRM2 and RRM3). Oligomerization of EDEN-BP is required for specific mRNA deadenylation and binding []. CELF-2 (also known as CUGBP2 or ETR-3) shares high sequence identity with CELF-1, but shows different binding specificity; it binds preferentially to sequences with UG repeats and UGUU motifs. It also binds to the 3'-UTR of cyclooxygenase-2 messages, affecting both translation and mRNA stability, and binds to apoB mRNA, regulating its C to U editing []. CELF-2 also contains three highly conserved RRMs. It binds to RNA via the first two RRMs, which are also important for localization in the cytoplasm. The splicing activation or repression activity of CELF-2 on some specific substrates is mediated by RRM1/RRM2. Both, RRM1 and RRM2 of CELF-2, can activate cardiac troponin T (cTNT) exon 5 inclusion. In addition, CELF-2 possesses a typical arginine and lysine-rich nuclear localization signal (NLS) in the C terminus, within RRM3 [].Proteins containing this motif also include Drosophila melanogaster Bruno protein, which plays a central role in regulation ofOskar (Osk) expression in flies. It mediates repression by binding to regulatory Bruno response elements (BREs) in the Osk mRNA 3' UTR []. The full-length Bruno protein contains three RRMs, two located in the N-terminal half of the protein and the third near the C terminus, separated by a linker region.
The beta (small) subunit of ribonucleotide reductase (RNR) is a member of a broad superfamily of ferritin-like diiron-carboxylate proteins. The RNR protein catalyzes the conversion of ribonucleotides to deoxyribonucleotides and is found in all eukaryotes, many prokaryotes, several viruses, and few archaea. The catalytically active form of RNR is a proposed alpha2-beta2 tetramer. The homodimeric alpha subunit (R1) contains the active site and redox active cysteines as well as the allosteric binding sites. The beta subunit (R2) contains a di-iron cluster that, in its reduced state, reacts with dioxygen to form a stable tyrosyl radical and a di-iron(III) cluster. This essential tyrosyl radical is proposed to generate a thiyl radical, located on a cysteine residue in the R1 active site that initiates ribonucleotide reduction. The beta subunit is composed of 10-13 helices, the eight longest helices form an α-helical bundle; some have two addition beta strands [, , , ].The beta-herpesvirus RNR R1 subunit homologues are catalytically inactive; the enzyme seem to function by inhibiting cellular adaptor protein RIP1 to block cellular signaling pathways involved in innate immunity and inflammation [].Yeast is unique in that it assembles both homodimers and heterodimers of RNR. The yeast heterodimer, Y2Y4, contains R2 (Y2) and a R2 homologue (Y4) that lacks the diiron centre and is proposed to only assist in cofactor assembly, and perhaps stabilize R1 (Y1) in its active conformation [, ]. In mammals, the active form of the enzyme is composed of two identical large subunits (RRM1) and two identical small subunits (RRM2 or its homologue RRM2B). RRM1 is the catalytic subunit, and RRM2 and RRM2B the regulatory subunits. RRM2B (also called p53R2) can be induced by p53 [, ].
The beta (small) subunit of ribonucleotide reductase (RNR) is a member of a broad superfamily of ferritin-like diiron-carboxylate proteins. The RNR protein catalyzes the conversion of ribonucleotides to deoxyribonucleotides and is found in all eukaryotes, many prokaryotes, several viruses, and few archaea. The catalytically active form of RNR is a proposed alpha2-beta2 tetramer. The homodimeric alpha subunit (R1) contains the active site and redox active cysteines as well as the allosteric binding sites. The beta subunit (R2) contains a di-iron cluster that, in its reduced state, reacts with dioxygen to form a stable tyrosyl radical and a di-iron(III) cluster. This essential tyrosyl radical is proposed to generate a thiyl radical, located on a cysteine residue in the R1 active site that initiates ribonucleotide reduction. The beta subunit is composed of 10-13 helices, the eight longest helices form an α-helical bundle; some have two addition beta strands [, , , ].The beta-herpesvirus RNR R1 subunit homologues are catalytically inactive; the enzyme seem to function by inhibiting cellular adaptor protein RIP1 to block cellular signaling pathways involved in innate immunity and inflammation [].Yeast is unique in that it assembles both homodimers and heterodimers of RNR. The yeast heterodimer, Y2Y4, contains R2 (Y2) and a R2 homologue (Y4) that lacks the diiron centre and is proposed to only assist in cofactor assembly, and perhaps stabilize R1 (Y1) in its active conformation [, ]. In mammals, the active form of the enzyme is composed of two identical large subunits (RRM1) and two identical small subunits (RRM2 or its homologue RRM2B). RRM1 is the catalytic subunit, and RRM2 and RRM2B the regulatory subunits. RRM2B (also called p53R2) can be induced by p53 [, ].This entry includes the ribonucleoside-diphosphate reductase small subunit from Herpesviruses.
This entry represents the RNA recognition motif 2 (RRM2) of type I poly(A)-binding proteins (PABPs).Poly(A)-binding proteins (PABPs) are highly conserved proteins that bind to the poly(A) tail present at the 3' ends of most eukaryotic mRNAs []. These highly conserved proteins are found only in eukaryotes; single-celled eukaryotes each have a single PABP, whereas humans have five and Arabidopis has eight. In humans, three lineages of PABP proteins are observed: cytoplasmic PABPs (PABPC1, PABPC3, and iPABP); nuclear PABP (PABPN1); and X-linked PABP (PABPC5) []. The mammalian PABPs contain four RNA recognition motifs (RRMs). RRM 1 and 2 are primarily responsible for the high-affinity binding to homopolymeric adenosines, while RRMs 3 and 4 can bind to nonhomopolymeric AU sequences []. Proteins containing this motif include:Polyadenylate-binding protein 1 (PABP-1 or PABPC1): PABP-1 is the major cytoplasmic PABP isoform in adult mouse somatic cells. It is able to bindsimultaneously to the cap-binding complex subunit eIF4G and to the poly(A) tail. Therefore, it has been suggested to play a role in altering the structure and/or function of the translation termination complex. It may have additional functions within the eukaryotic mRNA transcriptome. PABP-1 possesses an A-rich sequence in its 5'-UTR and allows binding of PABP and blockage of translation of its own mRNA []. Polyadenylate-binding protein 3 (PABP-3 or PABPC3): PABP-3 is a testis-specific poly(A)-binding protein specifically expressed in round spermatids. It is mainly found in mammalian and may play an important role in the testis-specific regulation of mRNA homeostasis. PABP-3 shows significant sequence similarity to PABP-1. However, it binds to poly(A) with a lower affinity than PABP-1. Dislike PABP-1, PABP-3 lacks the A-rich sequence in its 5'-UTR []. Polyadenylate-binding protein 4 (PABP-4 or APP-1 or iPABP): PABP-4 is an inducible poly(A)-binding protein (iPABP) that is primarily localized to the cytoplasm. It shows significant sequence similarity to PABP-1 as well. The RNA binding properties of PABP-1 and PABP-4 appear to be identical []. Polyadenylate-binding protein 5 (PABP-5 or PABPC5):PABP-5 is encoded by PABPC5 gene within the X-specific subinterval, and expressed in fetal brain and in a range of adult tissues in mammals, such as ovary and testis. It may play an important role in germ cell development []. Moreover, unlike other PABPs, PABP-5 contains only four RRMs, but lacks both the linker region and the CTD. Polyadenylate-binding protein 1-like (PABP-1-like or PABPC1L): orthologue of PABP-1.Polyadenylate-binding protein 1-like 2 (PABPC1L2 or RBM32): orthologue of PABP-1. Polyadenylate-binding protein 4-like (PABP-4-like or PABPC4L): orthologue of PABP-5. Polyadenylate-binding protein, cytoplasmic and nuclear (PABP or ACBP-67): PABP is a conserved poly(A) binding protein containing poly(A) tails that can be attached to the 3'-ends of mRNAs. The yeast PABP, also known as Pab1, and its homologues may play important roles in the initiation of translation and in mRNA decay []. Like vertebrate PABP-1, Pab1 contains four RRMs, a linker region, and a proline-rich CTD as well. The first two RRMs are mainly responsible for specific binding to poly(A). The proline-rich region may be involved in protein-protein interactions. The association of RRM2 of yeast Pab1 with eIF4G is a prerequisite for the poly(A) tail to stimulate the translation of mRNA in vitro []. Polyadenylate-binding protein Pes4 and Mip6.
