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bioRxiv · 10.1101/2020.10.19.344200

Structure of a transcribing RNA polymerase II-U1 snRNP complex

Zhang, S.·Aibara, S.·Vos, S. M.·Agafonov, D. E.·Lührmann, R.·Cramer, P.
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Abstract

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.

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Zhang, S., Aibara, S., Vos, S. M., Agafonov, D. E., Lührmann, R., Cramer, P.. 2020-10-20. Structure of a transcribing RNA polymerase II-U1 snRNP complex. https://doi.org/10.1101/2020.10.19.344200

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