Structural insights into spliceosome fidelity: DHX35-GPATCH1-mediated rejection of aberrant splicing substrates
The spliceosome, a highly dynamic macromolecular assembly, catalyzes the precise removal of introns from pre-mRNAs. Recent studies have provided comprehensive structural insights into the step-wise assembly, catalytic splicing and final disassembly of the spliceosome. However, the molecular details...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
28 February 2025
|
| In: |
Cell research
Year: 2025, Jahrgang: 35, Heft: 4, Pages: 296-308 |
| ISSN: | 1748-7838 |
| DOI: | 10.1038/s41422-025-01084-w |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41422-025-01084-w Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41422-025-01084-w 
|
| Verfasserangaben: | Yi Li, Paulina Fischer, Mengjiao Wang, Qianxing Zhou, Aixia Song, Rui Yuan, Wanyu Meng, Fei Xavier Chen, Reinhard Lührmann, Benjamin Lau, Ed Hurt, Jingdong Cheng |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 192463922X | ||
| 003 | DE-627 | ||
| 005 | 20250819230124.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 250505s2025 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41422-025-01084-w |2 doi | |
| 035 | |a (DE-627)192463922X | ||
| 035 | |a (DE-599)KXP192463922X | ||
| 035 | |a (OCoLC)1528045171 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Li, Yi |e VerfasserIn |0 (DE-588)1364599546 |0 (DE-627)1924640368 |4 aut | |
| 245 | 1 | 0 | |a Structural insights into spliceosome fidelity |b DHX35-GPATCH1-mediated rejection of aberrant splicing substrates |c Yi Li, Paulina Fischer, Mengjiao Wang, Qianxing Zhou, Aixia Song, Rui Yuan, Wanyu Meng, Fei Xavier Chen, Reinhard Lührmann, Benjamin Lau, Ed Hurt, Jingdong Cheng |
| 264 | 1 | |c 28 February 2025 | |
| 300 | |a 13 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 05.05.2025 | ||
| 520 | |a The spliceosome, a highly dynamic macromolecular assembly, catalyzes the precise removal of introns from pre-mRNAs. Recent studies have provided comprehensive structural insights into the step-wise assembly, catalytic splicing and final disassembly of the spliceosome. However, the molecular details of how the spliceosome recognizes and rejects suboptimal splicing substrates remained unclear. Here, we show cryo-electron microscopy structures of spliceosomal quality control complexes from a thermophilic eukaryote, Chaetomium thermophilum. The spliceosomes, henceforth termed B*Q, are stalled at a catalytically activated state but prior to the first splicing reaction due to an aberrant 5’ splice site conformation. This state is recognized by G-patch protein GPATCH1, which is docked onto PRP8-EN and -RH domains and has recruited the cognate DHX35 helicase to its U2 snRNA substrate. In B*Q, DHX35 has dissociated the U2/branch site helix, while the disassembly helicase DHX15 is docked close to its U6 RNA 3’-end substrate. Our work thus provides mechanistic insights into the concerted action of two spliceosomal helicases in maintaining splicing fidelity by priming spliceosomes that are bound to aberrant splice substrates for disassembly. | ||
| 650 | 4 | |a Cryoelectron microscopy | |
| 650 | 4 | |a Transcription | |
| 700 | 1 | |a Fischer, Paulina |d 1987- |e VerfasserIn |0 (DE-588)1131652533 |0 (DE-627)886286670 |0 (DE-576)488349559 |4 aut | |
| 700 | 1 | |a Wang, Mengjiao |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zhou, Qianxing |e VerfasserIn |4 aut | |
| 700 | 1 | |a Song, Aixia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Yuan, Rui |e VerfasserIn |4 aut | |
| 700 | 1 | |a Meng, Wanyu |e VerfasserIn |4 aut | |
| 700 | 1 | |a Chen, Fei Xavier |e VerfasserIn |4 aut | |
| 700 | 1 | |a Lührmann, Reinhard |e VerfasserIn |4 aut | |
| 700 | 1 | |a Lau, Benjamin |d 1980- |e VerfasserIn |0 (DE-588)1197332979 |0 (DE-627)167911915X |4 aut | |
| 700 | 1 | |a Hurt, Ed |d 1955- |e VerfasserIn |0 (DE-588)11021952X |0 (DE-627)729291863 |0 (DE-576)373308574 |4 aut | |
| 700 | 1 | |8 1\p |a Cheng, Jingdong |e VerfasserIn |0 (DE-588)1162226951 |0 (DE-627)102569791X |0 (DE-576)507279417 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell research |d [London] : Macmillan Publishers Limited, part of Springer Nature, 1990 |g 35(2025), 4, Seite 296-308 |h Online-Ressource |w (DE-627)350260435 |w (DE-600)2082402-6 |w (DE-576)306830132 |x 1748-7838 |7 nnas |a Structural insights into spliceosome fidelity DHX35-GPATCH1-mediated rejection of aberrant splicing substrates |
| 773 | 1 | 8 | |g volume:35 |g year:2025 |g number:4 |g pages:296-308 |g extent:13 |a Structural insights into spliceosome fidelity DHX35-GPATCH1-mediated rejection of aberrant splicing substrates |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s41422-025-01084-w |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://www.nature.com/articles/s41422-025-01084-w |x Verlag |z lizenzpflichtig |3 Volltext |
| 883 | |8 1\p |a cgwrk |d 20250802 |q DE-101 |u https://d-nb.info/provenance/plan#cgwrk | ||
| 951 | |a AR | ||
| 992 | |a 20250505 | ||
| 994 | |a 2025 | ||
| 998 | |g 11021952X |a Hurt, Ed |m 11021952X:Hurt, Ed |d 700000 |d 711000 |e 700000PH11021952X |e 711000PH11021952X |k 0/700000/ |k 1/700000/711000/ |p 11 | ||
| 998 | |g 1197332979 |a Lau, Benjamin |m 1197332979:Lau, Benjamin |d 700000 |d 711000 |e 700000PL1197332979 |e 711000PL1197332979 |k 0/700000/ |k 1/700000/711000/ |p 10 | ||
| 998 | |g 1131652533 |a Fischer, Paulina |m 1131652533:Fischer, Paulina |d 700000 |d 711000 |e 700000PF1131652533 |e 711000PF1131652533 |k 0/700000/ |k 1/700000/711000/ |p 2 | ||
| 999 | |a KXP-PPN192463922X |e 472001027X | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"language":["eng"],"title":[{"title":"Structural insights into spliceosome fidelity","subtitle":"DHX35-GPATCH1-mediated rejection of aberrant splicing substrates","title_sort":"Structural insights into spliceosome fidelity"}],"recId":"192463922X","origin":[{"dateIssuedDisp":"28 February 2025","dateIssuedKey":"2025"}],"type":{"media":"Online-Ressource","bibl":"article-journal"},"relHost":[{"type":{"media":"Online-Ressource","bibl":"periodical"},"recId":"350260435","origin":[{"dateIssuedDisp":"1990-","publisher":"Macmillan Publishers Limited, part of Springer Nature ; Institute of Biochemistry and Cell Biology","dateIssuedKey":"1990","publisherPlace":"[London] ; Shanghai"}],"id":{"eki":["350260435"],"issn":["1748-7838"],"zdb":["2082402-6"]},"disp":"Structural insights into spliceosome fidelity DHX35-GPATCH1-mediated rejection of aberrant splicing substratesCell research","physDesc":[{"extent":"Online-Ressource"}],"note":["Gesehen am 21.11.25","China-Zeitschriften-Code: CN31-1568","CAJ control code: XXBY"],"name":{"displayForm":["Zhong guo ke xue yuan shang hai sheng ming ke xue yan jiu yuan sheng wu hua xue yu xi bao sheng wu xue yan jiu suo; Zhong guo xi bao sheng wu xue xue hui"]},"pubHistory":["1.1990 -"],"title":[{"title":"Cell research","title_sort":"Cell research"}],"part":{"issue":"4","extent":"13","pages":"296-308","text":"35(2025), 4, Seite 296-308","year":"2025","volume":"35"},"language":["eng"]}],"note":["Gesehen am 05.05.2025"],"id":{"eki":["192463922X"],"doi":["10.1038/s41422-025-01084-w"]},"physDesc":[{"extent":"13 S."}],"name":{"displayForm":["Yi Li, Paulina Fischer, Mengjiao Wang, Qianxing Zhou, Aixia Song, Rui Yuan, Wanyu Meng, Fei Xavier Chen, Reinhard Lührmann, Benjamin Lau, Ed Hurt, Jingdong Cheng"]},"person":[{"display":"Li, Yi","given":"Yi","role":"aut","family":"Li"},{"family":"Fischer","display":"Fischer, Paulina","role":"aut","given":"Paulina"},{"family":"Wang","display":"Wang, Mengjiao","role":"aut","given":"Mengjiao"},{"display":"Zhou, Qianxing","given":"Qianxing","role":"aut","family":"Zhou"},{"family":"Song","role":"aut","given":"Aixia","display":"Song, Aixia"},{"family":"Yuan","display":"Yuan, Rui","given":"Rui","role":"aut"},{"display":"Meng, Wanyu","role":"aut","given":"Wanyu","family":"Meng"},{"given":"Fei Xavier","role":"aut","display":"Chen, Fei Xavier","family":"Chen"},{"role":"aut","given":"Reinhard","display":"Lührmann, Reinhard","family":"Lührmann"},{"role":"aut","given":"Benjamin","display":"Lau, Benjamin","family":"Lau"},{"family":"Hurt","role":"aut","given":"Ed","display":"Hurt, Ed"},{"display":"Cheng, Jingdong","role":"aut","given":"Jingdong","family":"Cheng"}]} | ||
| SRT | |a LIYIFISCHESTRUCTURAL2820 | ||