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Structure of a transcribing RNA polymerase II-U1 snRNP complex

By Suyang Zhang, Shintaro Aibara, Seychelle M. Vos, Dmitry E Agafonov, Reinhard L├╝hrmann, Patrick Cramer

Posted 20 Oct 2020
bioRxiv DOI: 10.1101/2020.10.19.344200

To initiate co-transcriptional splicing, RNA polymerase II (Pol II) recruits U1 small nuclear ribonucleoprotein particle (U1 snRNP) to nascent pre-mRNA. Here we report the cryo-EM 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 5' splice site in pre-mRNA near the RNA exit site of Pol II. Extension of pre-mRNA retains the 5' splice site, leading to formation of an intron loop. Loop formation may facilitate scanning of the nascent pre-mRNA for the 3' splice site and enable prespliceosome assembly and functional pairing of distant intron ends. Our results provide a starting point for a mechanistic analysis of co-transcriptional splicing and the biogenesis of mRNA isoforms during alternative splicing. ### Competing Interest Statement The authors have declared no competing interest.

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