Abstract
U5 snRNP is a complex particle essential for RNA splicing. U5 snRNPs undergo intricate biogenesis that ensures that only a fully mature particle assembles into a splicing competent U4/U6•U5 tri-snRNP and enters the splicing reaction. During splicing, U5 snRNP is substantially rearranged and leaves as a U5/PRPF19 post-splicing particle, which requires re-generation before the next round of splicing. Here, we show that a previously uncharacterized protein TSSC4 is a component of U5 snRNP that promotes tri-snRNP formation. We provide evidence that TSSC4 associates with U5 snRNP chaperones, U5 snRNP and the U5/PRPF19 particle. Specifically, TSSC4 interacts with U5-specific proteins PRPF8, EFTUD2 and SNRNP200. We also identified TSSC4 domains critical for the interaction with U5 snRNP and the PRPF19 complex, as well as for TSSC4 function in tri-snRNP assembly. TSSC4 emerges as a specific chaperone that acts in U5 snRNP de novo biogenesis as well as post-splicing recycling.
Highlights
U5 small nuclear ribonucleoprotein particles (snRNPs) is a complex particle essential for RNA splicing
We identified several U5 chaperones such as AAR2, ZNHIT2, RUVBL1, RUVBL2, and ECD and a putative chaperone EAPP that has been shown to interact with U5 proteins PRPF8 and EFTUD212,15,17
We show that TSSC4 interacts (Fig. 1) and co-sediments (Fig. 2) with the U5 snRNP but we did not find any indication that TSSC4 is a stable component of the U4/U6U5 tri-snRNP
Summary
U5 snRNP is a complex particle essential for RNA splicing. U5 snRNPs undergo intricate biogenesis that ensures that only a fully mature particle assembles into a splicing competent U4/U6U5 tri-snRNP and enters the splicing reaction. TSSC4 interacts with U5-specific proteins PRPF8, EFTUD2 and SNRNP200. TSSC4 emerges as a specific chaperone that acts in U5 snRNP de novo biogenesis as well as post-splicing recycling. Over 160 proteins and 5 small noncoding nuclear RNAs (snRNAs) are involved in spliceosome formation and rearrangements during RNA splicing[1]. SnRNAs together with associated proteins form small nuclear ribonucleoprotein particles (snRNPs), which are basic building blocks of the spliceosome. Sm ring assembly on U5 snRNA is promoted and controlled by SMN and PRMT5 complexes in the cytoplasm and the core snRNP (U5 snRNA+7 Sm proteins) is imported to the nucleus where it interacts with additional U5 proteins[3,4,5,6,7]. Four of the U5-specific proteins PRPF8/U5-220K, SNRNP200/hBrr2/U5-200K, EFTUD2/
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