Long Noncoding RNA MALAT1 Controls Cell Cycle Progression

The mammalian genome encodes large number of long non protein-coding RNAs (lncRNAs). These lncRNAs are suggested to regulate key biological processes (including cellular proliferation and differentiation), and aberrant expression of these is associated with cancer. However, only a few of these lncRNAs have been functionally validated in biological or disease processes. MALAT1, an abundant nuclear-retained lncRNA, is overexpressed in several cancers, and its elevated expression has been associated with hyper-proliferation and metastasis. However, the underlying mechanism behind this deregulation and its association with cancer is poorly understood.

Here, researchers at the University of Illinois at Urbana-Champaign, establish the role of MALAT1 in the cell cycle pathway and propose the molecular mechanism of its function during normal cell cycle progression. MALAT1 RNA levels are differentially regulated and critical for normal cell cycle progression. Depletion of MALAT1 results in cell cycle arrest with significantly reduced cellular proliferation, simultaneously leading to activation of p53 and its target genes. Further, the accurate levels of MALAT1 in the cell are extremely crucial for expression and activity of the oncogenic transcription factor B-MYB, which is involved in G2/M progression. Our data indicates that the cancer-associated MALAT1 RNA regulates cellular proliferation by modulating the expression and/or pre-mRNA processing of cell cycle–regulated transcription factors.

• Tripathi V, Shen Z, Chakraborty A, Giri S, Freier SM, et al. (2013) Long Noncoding RNA MALAT1 Controls Cell Cycle Progression by Regulating the Expression of Oncogenic Transcription Factor B-MYB. PLoS Genet 9(3),  e1003368. [article]