Long Noncoding RNA MALAT1 Controls Cell Cycle Progression by Regulating the Expression of Oncogenic Transcription Factor B-MYB

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. © 2013 tripathi et al.