7qdz
From Proteopedia
80S-bound human SKI complex in the closed state
Structural highlights
FunctionSKI8_HUMAN Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency (PubMed:16307923, PubMed:19952111, PubMed:20178742). PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1 (PubMed:16307923, PubMed:19952111, PubMed:20178742). PAF1C is required for transcription of Hox and Wnt target genes (PubMed:16307923, PubMed:19952111, PubMed:20178742). PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL (PubMed:16307923, PubMed:19952111, PubMed:20178742). PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3) (PubMed:16307923, PubMed:19952111, PubMed:20178742). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription (PubMed:16307923, PubMed:19952111, PubMed:20178742). PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors (PubMed:16307923, PubMed:19952111, PubMed:20178742). In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription (PubMed:16307923, PubMed:19952111, PubMed:20178742). Required for mono- and trimethylation on histone H3 'Lys-4' (H3K4me3), dimethylation on histone H3 'Lys-79' (H3K4me3). Required for Hox gene transcription (PubMed:16307923, PubMed:19952111, PubMed:20178742). Also acts as a component of the SKI complex, a multiprotein complex that assists the RNA-degrading exosome during the mRNA decay and quality-control pathways (PubMed:16024656, PubMed:32006463, PubMed:35120588). The SKI complex catalyzes mRNA extraction from 80S ribosomal complexes in the 3'-5' direction and channels mRNA to the cytosolic exosome for degradation (PubMed:32006463, PubMed:35120588). SKI-mediated extraction of mRNA from stalled ribosomes allow binding of the Pelota-HBS1L complex and subsequent ribosome disassembly by ABCE1 for ribosome recycling (PubMed:32006463).[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedThe superkiller (SKI) complex is the cytoplasmic co-factor and regulator of the RNA-degrading exosome. In human cells, the SKI complex functions mainly in co-translational surveillance-decay pathways, and its malfunction is linked to a severe congenital disorder, the trichohepatoenteric syndrome. To obtain insights into the molecular mechanisms regulating the human SKI (hSKI) complex, we structurally characterized several of its functional states in the context of 80S ribosomes and substrate RNA. In a prehydrolytic ATP form, the hSKI complex exhibits a closed conformation with an inherent gating system that effectively traps the 80S-bound RNA into the hSKI2 helicase subunit. When active, hSKI switches to an open conformation in which the gating is released and the RNA 3' end exits the helicase. The emerging picture is that the gatekeeping mechanism and architectural remodeling of hSKI underpin a regulated RNA channeling system that is mechanistically conserved among the cytoplasmic and nuclear helicase-exosome complexes. The human SKI complex regulates channeling of ribosome-bound RNA to the exosome via an intrinsic gatekeeping mechanism.,Kogel A, Keidel A, Bonneau F, Schafer IB, Conti E Mol Cell. 2022 Feb 17;82(4):756-769.e8. doi: 10.1016/j.molcel.2022.01.009. Epub , 2022 Feb 3. PMID:35120588[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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