SMN is essential for the biogenesis of U7 Small nuclear ribonucleoprotein and 3'-end formation of Histone mRNAs

Sarah Tisdale, Francesco Lotti, Luciano Saieva, James P. VanMeerbeke, Thomas O. Crawford, Charlotte J. Sumner, George Z. Mentis, Livio Pellizzoni

Research output: Contribution to journalArticle

Abstract

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by a deficiency in the survival motor neuron (SMN) protein. SMN mediates the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs) and possibly other RNPs. Here, we investigated SMN requirement for the biogenesis and function of U7-an snRNP specialized in the 3@-end formation of replication-dependent histone mRNAs that normally are not polyadenylated. We show that SMN deficiency impairs U7 snRNP assembly and decreases U7 levels in mammalian cells. The SMN-dependent U7 reduction affects endonucleolytic cleavage of histone mRNAs leading to abnormal accumulation of 3@-extended and polyadenylated transcripts followed by downstream changes in histone gene expression. Importantly, SMN deficiency induces defects of histone mRNA 3@-end formation in both SMA mice and human patients. These findings demonstrate that SMN is essential for U7 biogenesis and histone mRNA processing invivo and identify an additional RNA pathway disrupted in SMA.

Original languageEnglish (US)
Pages (from-to)1187-1195
Number of pages9
JournalCell Reports
Volume5
Issue number5
DOIs
StatePublished - Dec 12 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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