期刊
EMBO JOURNAL
卷 31, 期 20, 页码 4035-4044出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2012.252
关键词
polyadenylation; U1 site; 3' UTR mutation
资金
- DFG [BO 2512/2-1, BO 3006/2-1]
- Israeli-Lower Saxony cooperation [VWZN2628]
- DFG Gottfried-Wilhelm-Leibniz program
- BMBF E-RARE program
Biallelic mutations in the untranslated regions (UTRs) of mRNAs are rare causes for monogenetic diseases whose mechanisms remain poorly understood. We investigated a 3'UTR mutation resulting in a complex immunodeficiency syndrome caused by decreased mRNA levels of p14/robld3 by a previously unknown mechanism. Here, we show that the mutation creates a functional 50 splice site (SS) and that its recognition by the spliceosomal component U1 snRNP causes p14 mRNA suppression in the absence of splicing. Histone processing signals are able to rescue p14 expression. Therefore, the mutation interferes only with canonical poly(A)-site 3' end processing. Our data suggest that U1 snRNP inhibits cleavage or poly(A) site recognition. This is the first description of a 3'UTR mutation that creates a functional 5'SS causative of a monogenetic disease. Moreover, our data endorse the recently described role of U1 snRNP in suppression of intronic poly(A) sites, which is here deleterious for p14 mRNA biogenesis. The EMBO Journal (2012) 31, 4035-4044. doi:10.1038/emboj.2012.252; Published online 11 September 2012
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