The integrity of the U12 snRNA 3 ' stem-loop is necessary for its overall stability

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Norppa , A J & Frilander , M J 2021 , ' The integrity of the U12 snRNA 3 ' stem-loop is necessary for its overall stability ' , Nucleic Acids Research , vol. 49 , no. 5 , pp. 2835-2847 . https://doi.org/10.1093/nar/gkab048

Title: The integrity of the U12 snRNA 3 ' stem-loop is necessary for its overall stability
Author: Norppa, Antto J.; Frilander, Mikko J.
Contributor organization: Institute of Biotechnology
Biosciences
Date: 2021-03-18
Language: eng
Number of pages: 13
Belongs to series: Nucleic Acids Research
ISSN: 0305-1048
DOI: https://doi.org/10.1093/nar/gkab048
URI: http://hdl.handle.net/10138/330572
Abstract: Disruption of minor spliceosome functions underlies several genetic diseases with mutations in the minor spliceosome-specific small nuclear RNAs (snRNAs) and proteins. Here, we define the molecular outcome of the U12 snRNA mutation (84C>U) resulting in an early-onset form of cerebellar ataxia. To understand the molecular consequences of the U12 snRNA mutation, we created cell lines harboring the 84C>T mutation in the U12 snRNA gene (RNU12). We show that the 84C>U mutation leads to accelerated decay of the snRNA, resulting in significantly reduced steady-state U12 snRNA levels. Additionally, the mutation leads to accumulation of 3 '-truncated forms of U12 snRNA, which have undergone the cytoplasmic steps of snRNP biogenesis. Our data suggests that the 84C>U-mutant snRNA is targeted for decay following reimport into the nucleus, and that the U12 snRNA fragments are decay intermediates that result from the stalling of a 3 '-to-5 ' exonuclease. Finally, we show that several other single-nucleotide variants in the 3 ' stem-loop of U12 snRNA that are segregating in the human population are also highly destabilizing. This suggests that the 3 ' stem-loop is important for the overall stability of the U12 snRNA and that additional disease-causing mutations are likely to exist in this region.
Subject: SMALL NUCLEAR-RNA
5 SPLICE-SITE
DEVELOPMENTAL DISORDER
MINOR SPLICEOSOME
SURVEILLANCE PATHWAY
DEGRADATION PATHWAY
TRUNCATED FORMS
QUALITY-CONTROL
IN-VIVO
PROTEIN
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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