miR-137
miR-137 | |
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Metazoa; | |
PDB structures | PDBe |
In molecular biology, miR-137 (or microRNA-137) is a short
Recent genome-wide association studies (GWAS) have provided evidence to suggest that single nucleotide polymorphisms in the vicinity of the MIR137 gene are statistically associated with schizophrenia and other psychiatric disorders.[1][2]
miR-137 is shown to regulate neural stem cell proliferation and differentiation in mouse embryonic stem cells, and neuronal maturation, including regulation of dendrite length, branch points, end points, and spine density in mouse adult hippocampal neuroprogenitor-derived and mouse fetal hippocampus neurons. Decreased spine density has also been observed in the dorsolateral cortex of patients with schizophrenia.
miR-137 belongs to the miR-137 clan (a clan is group of two or more RNA families that have arisen from a single evolutionary origin, as derived from their related structure and function). The miR-137 clan contains two members: miR-137 and miR-234; the total number of RNA domains in the clan is 112.
Chromosomal location and transcription
miR-137 is located on
The post-transcriptional processing of microRNA-137 can be altered by presence of a 15-bp variable nucleotide tandem repeat in the primary miRNA transcript, which leads to change in folding and the secondary structure of miR-137. This alteration is believed to cause inefficient processing of miR-137 to its mature form, and serve as a mechanism to downregulate miR-137 expression in various human melanoma cell lines.
Expression pattern
miR-137 has been reported to be enriched in neurons. In particular,
miR-137 is also found to be constitutively expressed in normal colonic epithelium in humans.[5]
Epigenetic regulation and cancers
miR-137 is embedded within a
miR-137 is epigenetically silenced in colorectal adenomatous tissues to the same extent as in colorectal cancer tissues, suggesting that methylation of miRNA is an early event in colorectal carcinogenesis.[5]
Analysis of promoter methylation in oral rinses of patients with squamous cell carcinoma of the head and neck showed that miR-137 methylation is associated with female gender and inversely associated with
Targets
Several target genes of miR-137 have been documented and shown to play important roles in various human cancers, cell cycle signalling and mouse embryonic stem cell development.
Balaguer et al. identified a list of 32 genes targeted by miR-137 by cross-referencing the global gene expression analysis of
Liu et al. further showed that miR-137 targets Cdc42 (cell division cycle 42), a well-known member of the
miR-137 has also been shown to directly inhibits
Another notable target of miR-137 is
In mouse embryonic stem cells (ESCs), Jarid1b (also known as KDM5b, a histone H3 Lysine 4 demethylase) has recently been shown to be another direct target of miR-137. Jarid1b is frequently expressed early in mouse embryonic development and is thought to maintain the expression of undifferentiated ESC markers. By suppressing Jarid1b protein level, miR-137 is believed to play a role in modulating the differentiated state of mouse ESCs.[13]
Stephan Ripke et al.[1] have identified fourteen target sites predicted by TargetScan:[14] C6orf47 (open reading frame of chromosome 6), HLA-DQA1 (Major histocompatibility complex, class II, DQ alpha 1), TNXB (A member of the tenascin family, also known as hexabrachion-like protein is a glycoprotein that is expressed in connective tissues including skin, joints and muscles) VARS (Valyl-tRNA synthetase), WBP1L (WW domain binding protein 1-like), CACNA1C (Calcium channel, voltage-dependent, L type, alpha 1C subunit), DPYD (Dihydropyrimidine dehydrogenase [NADP+]), CACNB2 (Voltage-dependent L-type calcium channel subunit beta-2), TSSK6 (Testis-Specific Serine Kinase 6), NT5DC2 (Cytosolic 5'-nucleotidase), PITPNM2 (Membrane-associated phosphatidylinositol transfer protein 2), SBNO1 (strawberry notch homolog 1), ZEB2 (Zinc finger E-box-binding homeobox 2) and PRKD3 (Serine/threonine-protein kinase D3).
Neault et al., a tumour suppressor and positive regulator p53 expression. It was observed that miR-137 expression is lost in Ras-dependent pancreatic cancer, and that restoration of its expression leads to cellular growth arrest and senescence in pancreatic cancer cells.
See also
References
Further reading
- Landgraf P, Rusu M, Sheridan R, et al. (June 2007). "A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing". Cell. 129 (7): 1401โ14. PMID 17604727.
- Griffiths-Jones S; et al. (2006). "miRBase: microRNA sequences, targets and gene nomenclature". Nucleic Acids Res. 34 (90001): D140โ4. PMID 16381832.
- Kim, AH; Parker, EK; Williamson, V; McMichael, GO; Fanous, AH; Vladimirov, VI (October 2012). "Experimental validation of candidate schizophrenia gene ZNF804A as target for hsa-miR-137". Schizophrenia Research. 141 (1): 60โ4. PMID 22883350.