title: Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB.
abstract: The long noncoding MALAT1 RNA is upregulated in cancer tissues and its elevated expression is associated with hyper-proliferation, but the underlying mechanism is poorly understood. We demonstrate that MALAT1 levels are regulated during normal cell cycle progression. Genome-wide transcriptome analyses in normal human diploid fibroblasts reveal that MALAT1 modulates the expression of cell cycle genes and is required for G1/S and mitotic progression. Depletion of MALAT1 leads to activation of p53 and its target genes. The cell cycle defects observed in MALAT1-depleted cells are sensitive to p53 levels, indicating that p53 is a major downstream mediator of MALAT1 activity. Furthermore, MALAT1-depleted cells display reduced expression of B-MYB (Mybl2), an oncogenic transcription factor involved in G2/M progression, due to altered binding of splicing factors on B-MYB pre-mRNA and aberrant alternative splicing. In human cells, MALAT1 promotes cellular proliferation by modulating the expression and/or pre-mRNA processing of cell cycle-regulated transcription factors. These findings provide mechanistic insights on the role of MALAT1 in regulating cellular proliferation.
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Vidisha
authors.initials: V
authors.lastname: Tripathi
authors.forename: Zhen
authors.initials: Z
authors.lastname: Shen
authors.forename: Arindam
authors.initials: A
authors.lastname: Chakraborty
authors.forename: Sumanprava
authors.initials: S
authors.lastname: Giri
authors.forename: Susan M
authors.initials: SM
authors.lastname: Freier
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wu
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
authors.forename: Supriya G
authors.initials: SG
authors.lastname: Prasanth
authors.forename: Ashish
authors.initials: A
authors.lastname: Lal
authors.forename: Kannanganattu V
authors.initials: KV
authors.lastname: Prasanth
mesh_terms: D017398:Alternative Splicing; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C557041:MALAT1 long non-coding RNA, human; C064352:MYBL2 protein, human; D012322:RNA Precursors; D062085:RNA, Long Noncoding; C495901:TP53 protein, human; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53
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