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Role of cancer‐associated nuclear‐retained RNA in pre‐mRNA splicing regulation
Author(s) -
Prasanth Kannanganattu V,
Tripathi Vidisha,
Zong Xinying,
Shen Zhen,
Prasanth Supriya G
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.203.2
Subject(s) - rna splicing , alternative splicing , malat1 , cell cycle , microbiology and biotechnology , biology , senescence , rna , messenger rna , gene expression , gene , population , rna binding protein , genetics , long non coding rna , demography , sociology
In eukaryotic cells, long ncRNAs (lncRNAs) play roles in crucial cellular processes and their aberrant expression is linked to several diseases. The cancer‐associated MALAT1 is an lncRNA that interacts with SR splicing factors, regulates SR‐protein activity and modulates alternative splicing. MALAT1 displays cell cycle‐regulated expression, with low levels during G1 and significantly elevated levels during G1/S transition. MALAT1 is required for entry into S‐phase progression, as MALAT1‐depleted human primary cells show defects in G1 to S‐phase transition. Significant population of MALAT1‐depleted cells undergoes senescence, with characteristicβ‐gal positive labeling and increased expression of senescence‐associated genes. Our results indicate that MALAT1 acts like a “molecular sponge” and titrates the functional level of SR proteins during cell cycle. This in turn facilitates alternative splicing of specific pre‐mRNAs involved in cell cycle progression.