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Trans splicing involves a novel form of small nuclear ribonucleoprotein particles

Nature volume 335, pages 559–562 (1988)Cite this article

Abstract

The trans-splicing reaction occurring in trypanosomes and related species1–4 as well as in the nematode Caenorhabditis elegans5 involves the transfer of a 5' exon from a spliced leader transcript (SL RNA) to a precursor messenger RNA transcript with a 3' splice acceptor site. This seems to take place in the same nuclear compartment as normal cis splicing and proceeds through Y-branched intermediates6,7 analogous to the lariats formed in cis splicing. The cellular machinery catalysing cis and trans splicing8,9,10 might therefore be expected to share some components, particularly in the nematode where some mRNAs are produced by both cis and trans splicing5. We generated possible secondary structures for the SL RNAs of several species and found they were remarkably similar although neither nucleotide sequence nor length is conserved. Each contained three stem-loops; strikingly the 5' splice site is adjacent to the turn of the most 5' loop and an Sm-binding consensus sequence11 is found between the second and third stem-loops. Sm is an antigen associated with small nuclear ribonucleoprotein particles (snRNPs). When incubated in HeLa cell nuclear extracts, SL RNAs become immunoprecipitable by anti-Sm, but not by other autoantibodies directed against proteins of mammalian snRNPs12,13. We propose that SL RNAs have a dual function in the trans splicing process: they consist of a 5' exon covalently linked to an snRNA-like sequence and seem likely to exist as Sm snRNP particles (SL snRNPs) within the cell. Just as the RNA in the U1 snRNP base-pairs with the 5' splice site14,15, rendering it susceptible to attack in the cis-splicing reaction16, so might the SL snRNP autonomously activate its own 5' splice site and thereby eliminate the need for a U1-like snRNP in the trans-splicing machinery.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, Department of Molecular Biophysics and Biochemistry, Yale University, 333 Cedar Street, New Haven, Connecticut, 06510, USA

    James P. Bruzik & Joan A. Steitz

  2. Synergen Inc., 1885 33rd Street, Boulder, Colorado, 80301, USA

    Kevin Van Doren & David Hirsh

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  1. James P. Bruzik
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  2. Kevin Van Doren
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  3. David Hirsh
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Bruzik, J., Doren, K., Hirsh, D. et al. Trans splicing involves a novel form of small nuclear ribonucleoprotein particles. Nature 335, 559–562 (1988). https://doi.org/10.1038/335559a0

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