UPF1 (or regulator of nonsense transcripts 1 homologue) is an essential RNA helicase that detects mRNAs containing premature stop codons and triggers their degradation. Together with UPF2 and UPF3, forms a surveillance complex, in which UPF2 acts as a bridge between UPF1 and UPF3. UPF2 and UPF3 are nonenzymatic components of the complex that stimulate the activity of UPF1 []. UPF1 has a N-terminal cysteine/histidine-rich zinc-binding domain (CH/ZBD), a regulatory 1B domain, followed by a helicase core that belongs to superfamily 1 (SF1).This is 1B domain of UPF1 which has a regulatory role. It suffers conformational changes from an inhibitory state to a transition-state complex that modulate RNA binding [, ].
UPF1 (or regulator of nonsense transcripts 1 homologue) is an essential RNA helicase that detects mRNAs containing premature stop codons and triggers their degradation. Together with UPF2 and UPF3, forms a surveillance complex, in which UPF2 acts as a bridge between UPF1 and UPF3. UPF2 and UPF3 are nonenzymatic components of the complex that stimulate the activity of UPF1 []. UPF1 has a N-terminal cysteine/histidine-rich zinc-binding domain (CH/ZBD), a regulatory 1B domain, followed by a helicase core that belongs to superfamily 1 (SF1).This is the N-terminal CH/ZBD which contains 3 zinc binding motifs that interacts with UPF2 and it also has a cis-inhibitory effect on the ATPase activity. After binding to UPF2, the CH/ZBD suffers a large conformational change that causes the catalytic helicase domain to bind RNA less extensively and triggering its helicase activity [, ].
This entry includes Nmd2 from yeasts and UPF2 from animals. They are involved in the nonsense-mediated mRNA decay (NMD) pathway [, ]. In the human UPF complex (composed of UPF1/2/3), UPF2 and UPF3b cooperatively stimulate both ATPase and RNA helicase activities of UPF1 [].
SMG-1 plays a critical role in the mRNA surveillance mechanism known as non-sense mediated mRNA decay (NMD). NMD protects the cells from the accumulation of aberrant mRNAs with premature termination codons (PTCs) generated by genome mutations and by errors during transcription and splicing. SMG-1 phosphorylates Upf1, another central component of NMD, at the C terminus upon recognition of PTCs. The phosphorylation/dephosphorylation cycle of Upf1 is essential for promoting NMD []. In addition to its catalytic domain, SMG-1 contains a FATC (FRAP, ATM and TRRAP, C-terminal) domain at the C terminus. SMG-1 is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470kDa) []. This entry represents the SMG-1 catalytic domain.
The yeast helicase Sen1 is an ATP-dependent 5'->3' DNA/RNA helicase required for the expression and maturation of diverse classes of non-protein-coding RNAs like precursor tRNAs, rRNAs and small nuclear (snRNA) and nucleolar (snoRNA) RNAs [, ]and it also has an ATPase-dependent ability of promoting transcription termination in vitro []. Sen1 has a key role at replication forks during DNA replication to promote fork progression and chromosome stability []. Sen1 belongs to the superfamily 1B UPF1-like family of helicases with a common domain organisation: a N-terminal domain and a C-terminal domain which contains the SF1B helicase with two RecA domains (RecA1 and RecA2) and the classical helicase motifs involved in nucleic acid binding and ATP hydrolysis. It also contains two SF1B-specific subdomains (1B and 1C) that modulate RNA binding. This entry represents the 1B regulatory domain found in the helicase Sen1 from S. cerevisiae, which has a more elaborate topology of the 1B barrel domain from that of UPF1 [].
