Structure of a transcribing RNA polymerase II-U1 snRNP complex

To initiate cotranscriptional splicing, RNA polymerase II (Pol II) recruits the U1 small nuclear ribonucleoprotein particle (U1 snRNP) to nascent precursor messenger RNA (pre-mRNA). Here, we report the cryo-electron microscopy structure of a mammalian transcribing Pol II-U1 snRNP complex. The struct...

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Veröffentlicht in:Science (American Association for the Advancement of Science) 2021-01, Vol.371 (6526), p.305-309
Hauptverfasser: Zhang, Suyang, Aibara, Shintaro, Vos, Seychelle M, Agafonov, Dmitry E, Lührmann, Reinhard, Cramer, Patrick
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Sprache:eng
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Zusammenfassung:To initiate cotranscriptional splicing, RNA polymerase II (Pol II) recruits the U1 small nuclear ribonucleoprotein particle (U1 snRNP) to nascent precursor messenger RNA (pre-mRNA). Here, we report the cryo-electron microscopy structure of a mammalian transcribing Pol II-U1 snRNP complex. The structure reveals that Pol II and U1 snRNP interact directly. This interaction positions the pre-mRNA 5' splice site near the RNA exit site of Pol II. Extension of pre-mRNA retains the 5' splice site, leading to the formation of a "growing intron loop." Loop formation may facilitate scanning of nascent pre-mRNA for the 3' splice site, functional pairing of distant intron ends, and prespliceosome assembly. Our results provide a starting point for a mechanistic analysis of cotranscriptional spliceosome assembly and the biogenesis of mRNA isoforms by alternative splicing.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.abf1870