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Quality control of assembly-defective U1 snRNAs by decapping and 5'-to-3' exonucleolytic digestion.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2014 Aug 12; Vol. 111 (32), pp. E3277-86. Date of Electronic Publication: 2014 Jul 28. - Publication Year :
- 2014
-
Abstract
- The accurate biogenesis of RNA-protein complexes is a key aspect of eukaryotic cells. Defects in Sm protein complex binding to snRNAs are known to reduce levels of snRNAs, suggesting an unknown quality control system for small nuclear ribonucleoprotein (snRNP) assembly. snRNA quality control may also be relevant in spinal muscular atrophy, which is caused by defects in the survival motor neuron (SMN)1 gene, an assembly factor for loading the Sm complex on snRNAs and, when severely reduced, can lead to reduced levels of snRNAs and splicing defects. To determine how assembly-defective snRNAs are degraded, we first demonstrate that yeast U1 Sm-mutant snRNAs are degraded either by Rrp6- or by Dcp2-dependent decapping/5'-to-3' decay. Knockdown of the decapping enzyme DCP2 in mammalian cells also increases the levels of assembly-defective snRNAs and suppresses some splicing defects seen in SMN-deficient cells. These results identify a conserved mechanism of snRNA quality control, and also suggest a general paradigm wherein the phenotype of an "RNP assembly disease" might be suppressed by inhibition of a competing RNA quality control mechanism.
- Subjects :
- Animals
Endoribonucleases antagonists & inhibitors
Endoribonucleases genetics
Endoribonucleases metabolism
Gene Knockdown Techniques
HeLa Cells
Humans
Mice
Models, Biological
Mutation
NIH 3T3 Cells
Quality Control
RNA Splicing
RNA Stability genetics
RNA, Fungal genetics
RNA, Fungal metabolism
Ribonucleoproteins, Small Nuclear chemistry
Ribonucleoproteins, Small Nuclear metabolism
Survival of Motor Neuron 1 Protein antagonists & inhibitors
Survival of Motor Neuron 1 Protein genetics
Survival of Motor Neuron 1 Protein metabolism
RNA, Small Nuclear genetics
RNA, Small Nuclear metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 111
- Issue :
- 32
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 25071210
- Full Text :
- https://doi.org/10.1073/pnas.1412614111