Alternative exon definition events control the choice between nuclear retention and cytoplasmic export of U11/U12-65K mRNA

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http://hdl.handle.net/10138/199224

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Verbeeren , J , Verma , B , Niemela , E H , Yap , K , Makeyev , E V & Frilander , M J 2017 , ' Alternative exon definition events control the choice between nuclear retention and cytoplasmic export of U11/U12-65K mRNA ' , PLoS Genetics , vol. 13 , no. 5 , 1006824 . https://doi.org/10.1371/journal.pgen.1006824

Title: Alternative exon definition events control the choice between nuclear retention and cytoplasmic export of U11/U12-65K mRNA
Author: Verbeeren, Jens; Verma, Bhupendra; Niemela, Elina H.; Yap, Karen; Makeyev, Eugene V.; Frilander, Mikko J.
Contributor: University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Research Programs Unit
University of Helsinki, Institute of Biotechnology
Date: 2017-05
Language: eng
Number of pages: 28
Belongs to series: PLoS Genetics
ISSN: 1553-7404
URI: http://hdl.handle.net/10138/199224
Abstract: Cellular homeostasis of the minor spliceosome is regulated by a negative feed-back loop that targets U11-48K and U11/U12-65K mRNAs encoding essential components of the U12-type intron-specific U11/U12 di-snRNP. This involves interaction of the U11 snRNP with an evolutionarily conserved splicing enhancer giving rise to unproductive mRNA isoforms. In the case of U11/U12-65K, this mechanism controls the length of the 3' untranslated region (3'UTR). We show that this process is dynamically regulated in developing neurons and some other cell types, and involves a binary switch between translation-competent mRNAs with a short 3'UTR to non-productive isoforms with a long 3'UTR that are retained in the nucleus or/and spliced to the downstream amylase locus. Importantly, the choice between these alternatives is determined by alternative terminal exon definition events regulated by conserved U12-and U2-type 50 splice sites as well as sequence signals used for pre-mRNA cleavage and polyadenylation. We additionally show that U11 snRNP binding to the U11/U12-65K mRNA species with a long 3'UTR is required for their nuclear retention. Together, our studies uncover an intricate molecular circuitry regulating the abundance of a key spliceosomal protein and shed new light on the mechanisms limiting the export of non-productively spliced mRNAs from the nucleus to the cytoplasm.
Subject: U1 SNRNP
U12-TYPE INTRONS
GENE-EXPRESSION
MINOR SPLICEOSOME
QUALITY-CONTROL
DEVELOPMENTAL DISORDER
POLY(A) POLYMERASE
MAMMALIAN-CELLS
U11-59K PROTEIN
NERVOUS-SYSTEM
3111 Biomedicine
1184 Genetics, developmental biology, physiology
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