| Literature DB >> 33986153 |
Lisa Fish1,2,3,4, Matvei Khoroshkin1,2,3,4, Albertas Navickas1,2,3,4, Kristle Garcia1,2,3,4, Bruce Culbertson1,2,3,4, Benjamin Hänisch1,2,3,4, Steven Zhang1,2,3,4, Hoang C B Nguyen5, Larisa M Soto6,7, Maria Dermit8, Faraz K Mardakheh8, Henrik Molina9, Claudio Alarcón10,11, Hamed S Najafabadi6,7, Hani Goodarzi12,2,3,4.
Abstract
Aberrant alternative splicing is a hallmark of cancer, yet the underlying regulatory programs that control this process remain largely unknown. Here, we report a systematic effort to decipher the RNA structural code that shapes pathological splicing during breast cancer metastasis. We discovered a previously unknown structural splicing enhancer that is enriched near cassette exons with increased inclusion in highly metastatic cells. We show that the spliceosomal protein small nuclear ribonucleoprotein polypeptide A' (SNRPA1) interacts with these enhancers to promote cassette exon inclusion. This interaction enhances metastatic lung colonization and cancer cell invasion, in part through SNRPA1-mediated regulation of PLEC alternative splicing, which can be counteracted by splicing modulating morpholinos. Our findings establish a noncanonical regulatory role for SNRPA1 as a prometastatic splicing enhancer in breast cancer.Entities:
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Year: 2021 PMID： 33986153 PMCID： PMC8238114 DOI： 10.1126/science.abc7531
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728