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

By Vidisha Tripathi, Zhen Shen, Arindam Chakraborty, S. Giri, Susan M. Freier, Xiaolin Wu, Yongqing Zhang, M. Gorospe, S. Prasanth, A. Lal and 1 more. PLoS Genetics, 2013

745 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e401bea6bfe41625391728adf8be7609455d7fa0

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Citations in the corpus

Long Noncoding RNAs in Cardiovascular Diseases (2015, neutral): “that is consistent with the known cell cycle regulatory effect of MALAT1 in other cell types.(75,76) However, the cell cycle”
Long Noncoding RNA MALAT1 Regulates Endothelial Cell Function and Vessel Growth (2014, background): “Because silencing of MALAT1 by siRNA induced an interesting switch from a proliferative to a promigratory state of the endothelial cells resulting in an aberrant vessel sprouting under proangiogenic conditions, we next aimed to confirm the above observations using a different approach to silence MAL”
Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer (2016, background): “And MALAT1 is expressed in a cell cycle-dependent manner and is required for G1/S and mitotic progression [92].”
The rise of regulatory RNA (2014, background): “…but not stem cells in mammals 227,228 ; the nuclear-localized MALAT-1, which regulates alternative splicing 229 and cell cycle progression 230 ; Gomafu, which is expressed in an unknown subnuclear structure, possibly a specialized spliceosome, in a subset of neurons 231 , and has…”
ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases (2016, background): “The senescence-associated lncRNAs are differentially expressed in proliferating and senescent fibroblasts, as assessed by RNA sequencing [224–226].”