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-Structure paper
タイトル | Structural basis for competitive binding of productive and degradative co-transcriptional effectors to the nuclear cap-binding complex. |
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ジャーナル・号・ページ | Cell Rep, Vol. 43, Issue 1, Page 113639, Year 2024 |
掲載日 | 2024年1月3日 |
著者 | Etienne Dubiez / Erika Pellegrini / Maja Finderup Brask / William Garland / Anne-Emmanuelle Foucher / Karine Huard / Torben Heick Jensen / Stephen Cusack / Jan Kadlec / |
PubMed 要旨 | The nuclear cap-binding complex (CBC) coordinates co-transcriptional maturation, transport, or degradation of nascent RNA polymerase II (Pol II) transcripts. CBC with its partner ARS2 forms mutually ...The nuclear cap-binding complex (CBC) coordinates co-transcriptional maturation, transport, or degradation of nascent RNA polymerase II (Pol II) transcripts. CBC with its partner ARS2 forms mutually exclusive complexes with diverse "effectors" that promote either productive or destructive outcomes. Combining AlphaFold predictions with structural and biochemical validation, we show how effectors NCBP3, NELF-E, ARS2, PHAX, and ZC3H18 form competing binary complexes with CBC and how PHAX, NCBP3, ZC3H18, and other effectors compete for binding to ARS2. In ternary CBC-ARS2 complexes with PHAX, NCBP3, or ZC3H18, ARS2 is responsible for the initial effector recruitment but inhibits their direct binding to the CBC. We show that in vivo ZC3H18 binding to both CBC and ARS2 is required for nuclear RNA degradation. We propose that recruitment of PHAX to CBC-ARS2 can lead, with appropriate cues, to competitive displacement of ARS2 and ZC3H18 from the CBC, thus promoting a productive rather than a degradative RNA fate. |
リンク | Cell Rep / PubMed:38175753 |
手法 | EM (単粒子) |
解像度 | 3.19 - 3.46 Å |
構造データ | EMDB-16321, PDB-8by6: EMDB-17763, PDB-8pmp: EMDB-17784, PDB-8pnt: |
化合物 | ChemComp-GTG: ChemComp-MGT: |
由来 |
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キーワード | RNA BINDING PROTEIN (RNA結合タンパク質) / Nuclear cap-binding complex / NCBP3 / Pol II transcript metabolism / ARS2 / PHAX |