This entry represents the RNA recognition motif 2 (RRM2) of La-related protein 7 (LARP7). LARP7 is an oligopyrimidine-binding protein that binds to the highly conserved 3'-terminal U-rich stretch (3' -UUU-OH) of 7SK RNA. LARP7 is a stable component of the 7SK small nuclear ribonucleoprotein (7SK snRNP). It intimately associates with all the nuclear 7SK and is required for 7SK stability []. LARP7 also acts as a negative transcriptional regulator of cellular and viral polymerase II genes, acting by means of the 7SK snRNP system []. LARP7 plays an essential role in the inhibition of positive transcription elongation factor b (P-TEFb)-dependent transcription, which has been linked to the global control of cell growth and tumorigenesis [].LARP7 contains a La motif (LAM) and an RNA recognition motif (RRM1) at the N-terminal region, which mediates binding to the U-rich 3' terminus of 7SK RNA. LARP7 also carries another putative RRM domain at its C terminus (RRM2).
This entry represents the RNA recognition motif 1 (RRM1) of La-related protein 7 (LARP7), an oligopyrimidine-binding protein that binds to the highly conserved 3'-terminal U-rich stretch (3' -UUU-OH) of 7SK RNA. LARP7 is a stable component of the 7SK small nuclear ribonucleoprotein (7SK snRNP) []. It intimately associates with all the nuclear 7SK and is required for 7SK stability []. LARP7 also acts as a negative transcriptional regulator of cellular and viral polymerase II genes, acting by means of the 7SK snRNP system. It plays an essential role in the inhibition of positive transcription elongation factor b (P-TEFb)-dependent transcription, which has been linked to the global control of cell growth and tumorigenesis [, ].LARP7 contains a La motif (LAM) and an RNA recognition motif (RRM1) at the N-terminal region, which mediates binding to the U-rich 3' terminus of 7SK RNA. LARP7 also carries another putative RRM domain at its C terminus.
LARP7 is a component of the 7SK snRNP, a key factor in the regulation of RNA polymerase II transcription. 7SK functionality is dependent on the presence of LARP7, which is thought to stabilize the 7SK RNA by interacting with its 3' end. The release of 7SK RNA from P-TEFb/HEXIM/7SK complexes activates the cyclin-dependent kinase P-TEFb, which in turn phosphorylates the C-terminal domain of RNA pol II and mediates a transition into productive transcription elongation [].LARP7 belongs to a group of factors that share an N-terminal La-like domain followed by one or two RNA-recognition motifs (RRM) []. This entry represents the La-like domain.
This entry represents the atypical RRM, named xRRM, found in La and La-related proteins (LaRPs). They belong to an ancient superfamily of proteins that are conserved in nearly all eukaryotes, except Plasmodium. These proteins are broadly involved in critical processes of RNA use and metabolism in the nucleus and the cytoplasm. The LaRP superfamily is distinguished by a conserved bipartite RNA-binding unit called the La-module, composed by a Lupus antigen motif (LaM) followed by an RNA-Recognition motif (RRM). Beyond this, each LaRP family is characterized by distinct family specific domains and motifs that contribute to structure and function. Genuine La and La-related proteins group 7 (LARP7) bind to the non-coding RNAs transcribed by RNA polymerase III (RNAPIII), which end in UUU. The La-module of these proteins bind the UUU-3'OH, protecting the RNA from degradation, while other domains may be important for RNA folding or other functions. The La and LaRP7 protein families have a C-terminal domain that contains a novel class of atypical RRM, named xRRM (for atypical RRM with extended alpha3), which uses a unique mode of single- and double-strand RNA binding [, , , , ]. The overall fold of the xRRM is an RRM, but with several atypical features. Unusual features of the xRRM include the absence of conserved RNP1 and RNP2 aromatic sequences on the beta3 and beta1 strands, respectively, typically involved in nucleotide recognition; the presence of an additional helix alpha3 that lies across the β-sheet surface, where single-stranded nucleotides usually bind; and a C-terminal tail required for RNA binding that is disordered in the free xRRM but forms an alpha3 extension (alpha3x) on binding RNA. The front face of the xRRM consists of an antiparallel β-sheet with helix alpha3 lying across the β-sheet perpendicular to the β-strand axis. The back side of the xRRM consists of alpha helices. The xRRM interacts with both single- and double-stranded RNA using the β-sheet surface and the C-terminal tail, which forms a helical extension of alpha3 (alhpa3x) that binds to the RNA major groove [, , , , ].
