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  2. A nematode-specific ribonucleoprotein complex mediates interactions between the major nematode spliced leader snRNP and its target pre-mRNAs

A nematode-specific ribonucleoprotein complex mediates interactions between the major nematode spliced leader snRNP and its target pre-mRNAs

  • Nucleic Acids Res. 2024 Jul 8;52(12):7245-7260. doi: 10.1093/nar/gkae321.
Peter Eijlers 1 Mohammed Al-Khafaji 1 Eva Soto-Martin 1 Rotimi Fasimoye 1 David Stead 2 Marius Wenzel 3 Berndt Müller 1 Jonathan Pettitt 1
Affiliations

Affiliations

  • 1 School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD Scotland, UK.
  • 2 School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Rowett Institute, Foresterhill, Aberdeen AB25 2ZD Scotland, UK.
  • 3 School of Biological Sciences, University of Aberdeen, Aberdeen AB24 2TZ Scotland, UK.
Abstract

Spliced leader trans-splicing of pre-mRNAs is a critical step in the gene expression of many eukaryotes. How the spliced leader RNA and its target transcripts are brought together to form the trans-spliceosome remains an important unanswered question. Using immunoprecipitation followed by protein analysis via mass spectrometry and RIP-Seq, we show that the nematode-specific proteins, SNA-3 and SUT-1, form a complex with a set of enigmatic non-coding RNAs, the SmY RNAs. Our work redefines the SmY snRNP and shows for the first time that it is essential for nematode viability and is involved in spliced leader trans-splicing. SNA-3 and SUT-1 are associated with the 5' ends of most, if not all, nascent capped RNA polymerase II transcripts, and they also interact with components of the major nematode spliced leader (SL1) snRNP. We show that depletion of SNA-3 impairs the co-immunoprecipitation between one of the SL1 snRNP components, SNA-2, and several core spliceosomal proteins. We thus propose that the SmY snRNP recruits the SL1 snRNP to the 5' ends of nascent pre-mRNAs, an instrumental step in the assembly of the trans-spliceosome.

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