Long Non-Coding RNA <em>MALAT1</em> Regulates Gene Expression and Protein Function via Multiple Layer and Flexible Manners

Review Article

Austin J Pathol Lab Med. 2014;1(3): 5.

Long Non-Coding RNA MALAT1 Regulates Gene Expression and Protein Function via Multiple Layer and Flexible Manners

Xianyong Ma1*, Charles X Ma2, Cai Qiang3 and Xin Tang4

1Department of Pathology, Yale University School of Medicine, USA

2MD student, University of Connecticut School of Medicine, USA

3Department of Neurosurgery, Peoples Hospital of Wuhan University, China

4Department of Orthopedics Surgery, Peoples Hospital of Xiangxi, China

*Corresponding author: Xianyong Ma, Department of Pathology, Yale University School of Medicine, New Haven, CT, USA

Received: October 15, 2014; Accepted: October 30, 2014; Published: November 03, 2014


MALAT1; lncRNA; Gene expression and regulation; Mechanisms


The Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) is one of the most significant molecules of long non-coding RNA (lncRNA), also known as Nuclear Enriched Transcript2 (NEAT2). MALAT1 was first discovered as a prognostic marker for non-small cell lung carcinoma [1]. Soon after, researchers found MALAT1 is linked to other cancers such as endometrial cancer [2], breast cancer [3], cervical cancer [4], colorectal cancer [5], hepatocellular carcinoma [6], liver cancer [7], neuroblastoma [8], osteosarcoma [9], pancreatic cancer [10], prostate cancer [11], bladder cancer [12], gastric cancer [13] and etc. In addition to its role as a biomarker for many human tumors, MALAT1 was also identified as a critical regulatory molecule to control target gene expression, modify RNA and protein (enzyme) activity, as well as affect cellular distribution [14-16], consequently it is intimately associated with the regulation of cell growth and proliferation. Dysregulations of MALAT1 result in multiple tissue carcinogenesis as well as many other human disease processes [17-20]. As such the critical regulatory role and potential clinical implications of MALAT1 have attracted more and more attention recently [10,17]. This review will focus on the regulatory role and molecular mechanisms of MALAT1 on gene expression and biochemical function of proteins. In addition, the paper will put forward the concept that the regulatory mechanisms of lncRNA on the gene expression and target protein function are in multiple layer and flexible manner.

I: MALAT1 regulates the bioactivity of target proteins via direct protein-lncRNA interaction

The interaction of lncRNA with protein has been linked to the regulation of target protein bioactivity [21-25]. MALAT1 interacts with several Alternative-Splicing (AS) factors such as SRSF1, SRSF2 and SRSF5 [26], which belong to a family of Serine/Arginine (SR)- rich splicing factors to regulate pre-RNA AS. Typically, SRSF proteins contain an RNA Binding Domain (RBD, also known as an RNA Recognition Motif, RRM) and Arginine/Serine (RS)-rich domain required for protein-protein interaction. SRSFs also regulate tissue or cell specific alternative splicing through a concentration and phosphorylation dependent manner. Full length MALAT1, as an abundant lncRNA molecule is localized in nuclear speckles and nucleoplasm, interacting with a sub-set of SRSF proteins and modulating their sub-nuclear distribution. It regulates cellular levels as well as the ratio of phosphorylated versus dephosphorylated SR proteins. Therefore MALAT1 plays a role in controlling alternative splicing patterns of certain endogenous pre-mRNAs. Ji Q. et al [27] demonstrated MALAT1 over expression in human Colorectal Cancer Cells (CRC), and discovered that MALAT1 binds to SFPQ (PTB-associated splicing factor), thus releasing proto-oncoprotein PTBP2 from SFPQ/PTBP2 complex, the increased SFPQ-detached PTBP2 then promoted cell proliferation and migration. The regulatory mechanism of protein activity by the interaction of MALAT1 and functional protein or complex is shown in Figure 1.