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Journal Article

Structure of a transcribing RNA polymerase II–U1 snRNP complex

MPS-Authors
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Zhang,  S.
Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society;

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Aibara,  S.
Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society;

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Vos,  S. M.
Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society;

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Agafonov,  D.
Department of Cellular Biochemistry, MPI for biophysical chemistry, Max Planck Society;

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Lührmann,  R.
Department of Cellular Biochemistry, MPI for biophysical chemistry, Max Planck Society;

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Cramer,  P.
Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society;

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Citation

Zhang, S., Aibara, S., Vos, S. M., Agafonov, D., Lührmann, R., & Cramer, P. (2021). Structure of a transcribing RNA polymerase II–U1 snRNP complex. Science, 371(6526), 305-309. doi:10.1126/science.abf1870.


Cite as: http://hdl.handle.net/21.11116/0000-0007-D428-D
Abstract
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.