Spliceosomal small nuclear ribonucleoprotein particles (snRNPs) undergo a complex maturation pathway containing multiple steps in the nucleus and in the cytoplasm. snRNP biogenesis is strictly proofread and several quality control checkpoints are placed along the pathway. Here, we analyzed the fate of small nuclear RNAs (snRNAs) that are unable to acquire a ring of Sm proteins. We showed that snRNAs lacking the Sm ring are unstable and accumulate in P-bodies in an LSm1-dependent manner. We further provide evidence that defective snRNAs without the Sm binding site are uridylated at the 3' end and associate with DIS3L2 3'→5' exoribonuclease and LSm proteins. Finally, inhibition of 5'→3' exoribonuclease XRN1 increases association of ΔSm snRNAs with DIS3L2, which indicates competition and compensation between these two degradation enzymes. Together, we provide evidence that defective snRNAs without the Sm ring are uridylated and degraded by alternative pathways involving either DIS3L2 or LSm proteins and XRN1.

CEITEC Central European Institute of Technology Masaryk University Kamenice 5 A35 625 00 Brno Czech Republic

Faculty of Science Charles University 128 00 Prague Czech Republic

Laboratory of RNA Biology Institute of Molecular Genetics of the Czech Academy of Sciences Videnska 1083 14220 Prague Czech Republic

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Nucleic Acids Res. 2022 Nov 28;50(21):12597. doi: 10.1093/nar/gkac1154. PubMed

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Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control

The SMN complex drives structural changes in human snRNAs to enable snRNP assembly