Synergistic roles for human U1 snRNA stem-loops in pre-mRNA splicing
Wohlschlegel, James A.
AffiliationDepartment of Basic Medical Sciences, College of Medicine-Phoenix, University of Arizona
Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health-Phoenix, University of Arizona
MetadataShow full item record
PublisherInforma UK Limited
CitationMartelly, W., Fellows, B., Kang, P., Vashisht, A., Wohlschlegel, J. A., & Sharma, S. (2021). Synergistic roles for human U1 snRNA stem-loops in pre-mRNA splicing. RNA Biology.
Rights© 2021 Informa UK Limited, trading as Taylor & Francis Group.
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AbstractDuring spliceosome assembly, interactions that bring the 5′ and 3′ ends of an intron in proximity are critical for the production of mature mRNA. Here, we report synergistic roles for the stem-loops 3 (SL3) and 4 (SL4) of the human U1 small nuclear RNA (snRNA) in maintaining the optimal U1 snRNP function, and formation of cross-intron contact with the U2 snRNP. We find that SL3 and SL4 bind distinct spliceosomal proteins and combining a U1 snRNA activity assay with siRNA-mediated knockdown, we demonstrate that SL3 and SL4 act through the RNA helicase UAP56 and the U2 protein SF3A1, respectively. In vitro analysis using UV crosslinking and splicing assays indicated that SL3 likely promotes the SL4-SF3A1 interaction leading to enhancement of A complex formation and pre-mRNA splicing. Overall, these results highlight the vital role of the distinct contacts of SL3 and SL4 in bridging the pre-mRNA bound U1 and U2 snRNPs during the early steps of human spliceosome assembly. © 2021 Informa UK Limited, trading as Taylor & Francis Group.
Note12 month embargo; published online: 09 June 2021
VersionFinal accepted manuscript
SponsorsNational Institute of General Medical Sciences