Please input one-sentence summary here.
- 1 Annotated Information
- 2 Labs working on this lncRNA
- 3 References
- 4 Basic Information
- 5 Annotation (From lncRNAdb)
Malat1: Metastasis-associated lung adenocarcinoma transcript 1
Neat2: Nuclear enriched abundant transcript 2
Malat1 gene is localized in the intergenic region of the genome. It is about 8kb in length and the transcript has only one exon (1,2). The 3’-end of the transcript is a conserved tRNA-like sequence, which can be modified by RNase P and cleaved by RNase Z to yield another ncRNA, the cytoplasmic MALAT1-associated small cytoplasmic RNA (mascRNA) (3).
Malat1 is stable in human B cells (half-life: 16.5 h) (4) and Hela cells (half-life: about 7 h) (5), but is unstable in mouse 3T3 cells (half-life: 3 h) (4) and N2A cells ( half-life: 4 h) (4). MALAT-1 is generally stable in cancer cells, with the half-life ranging from ~ 9 h to > 12 h in various cancer cells (6). Xrn2, PM/Scl-75, PARN, and Mtr4, known nuclear RNases or RNA helicases, do not affect MALAT-1 degradation (6).
MALAT-1 localize predominately in the nucleus . In G2/M cell cycle phase, MALAT-1 transcripts partially translocate from the nucleus into the cytoplasm (4). RNPS1, SRm160, and IBP160 are found to contribute to the nuclear localization of MALAT-1 (5).
MALAT-1 could modulate mRNA alternative splicing via its interaction with the serine/arginine-rich (SR) family of nuclear phosphoproteins that are involved in the splicing machinery (6). However, splicing alterations were not found after Malat1 ablation in mice (7). Also, MALAT1 does not alter alternative splicing but actively regulates gene expression including a set of metastasis-associated genes in lung cancer cells (8). These results indicate that alternative functions for MALAT-1 may exist.
MALAT-1 is found to regulate cell cycle progress in G2/M phase (4,6), G1/S phase (9), and G0/G1 phase (10). It is not quite clear how MALAT-1 functions to regulate cell cycle, but MALAT-1 is found to interact with hnRNP C and facilitate the cytoplasmic translocation of hnRNP C, which is an important step for cells to progress through the G2/M phase.
MALAT1 could interact with the demethylated form of CBX4 (chromobox homolog 4), also referred to as Pc2 (polycomb 2), a component of the polycomb repressive complex 1 (PRC1). This interaction controls the relocalization of growth control genes between polycomb bodies and interchromatin granules, areas of silent or active gene expression, respectively. MALAT1 resides in these subnuclear structures and acts as an activator of gene expression potentially by mediating the assembly of coactivator complexes (11).
In vitro, it is found that MALAT-1 promotes epithelial–mesenchymal transition (EMT) of bladder cancer cells by activating Wnt signaling (12). MALAT-1 participates in cell differentiation and development (1,2).
In breast cancer cells, high concentration E2 treatment largely decreases MALAT-1 RNA level in an ERa independent way (16).
Disruption of p53 appears to play an important role in the up-regulation of MALAT-1 (17).
MALAT-1 was first identified as a prognostic marker for metastasis and patient survival in non-small cell lung cancer (NSCLC) (18). It is found to be overexpressed in various human tumors, including NSCLC (1), hepatocellular carcinomas (19), breast cancer (20), prostate cancer (10), melanoma (14), bladder cancer (12). Overexpression of MALAT-1 in cancer cells is closely associated with tumor growth and metastasis (8,14,18,21).
There is no significant difference in MALAT-1 lncRNA levels in normal pituitary tissues, invasive NFPAs (non-functioning pituitary adenomas), and non-invasive NFPAs, and no significant association between MALAT-1 expression and patient clinicopathological characteristics. (15).
MALAT-1 is highly and ubiquity expressed in various tissue (13), including both cancer tissues and normal tissues, such as brain (13).
|Primer||Forward primer||Reverse primer|
|RT-PCR||5'-AAAGCAAGGTCTCCCCACAAG-3'||5'-GGTCTGTGCTAGATCAAAAGGCA-3' ( )|
|5'-CTTCCCTAGGGGATTTCAGG-3'||5'-GCCCACAGGAACAAGTCCTA-3' ( )|
|cDNA amplication||5'-GTAGGGCCCTCCATGGCGATTTGCCTTGTGAGCAC-3'||5'-GAGCTCGAGGTCCTGAAGACAGATTAGTAGTCAAAGC-3' |
Allelic Information and Variation
Please input allelic information and variation information here.
MALAT-1 is highly conserved over its full length (~8 kb) across mammals (13).
MALAT-1 is an 8-knt-long macromolecule that can form a complex structure to recruit many different protein factors for functionality. MALAT-1 is found to interact with hnRNP C and facilitate its cytoplasmic translocation in the G2/M phase, thereby regulating the progress of the cell cycle (4).
You can also add sub-section(s) at will.
Labs working on this lncRNA
Please input related labs here.
Please input cited references here.
Annotation (From lncRNAdb)
|Characteristics|| Intergenic ~7kb single exon transcript (Ji (2003), Hutchinson (2007)).|
A conserved tRNA-like sequence at the 3' end is cleaved off and processed to generated a short tRNA-like ncRNA mascRNA (MALAT1-associated small cytoplasmic RNA) (Wilusz (2008)).
Post transcriptional processing of Malat1 therefore allows two ncRNAs to be created from the one original transcript (Wilusz (2008)).
|Expression|| Both Malat1 and the processed mascRNA transcript are expressed in a wide range of tissues (Ji (2003), Hutchinson (2007), Wilusz (2008)), Bernard (2010), (Ulitsky (2011)).|
Malat1 is highly expressed in the brain. RNA fluorescence in-situ hybridization (RNA-FISH) on adult mouse brain sections showed high expression of nuclear-localized Malat1 transcripts in pyramidal neurons of the hippocampus, Purkinje cells of the cerebellum and neurons of the substantia nigra and motoneurons, but very low levels in non-neuronal cells (Bernard (2010)). In the hippocampus and in Purkinje cells, Malat1 was first detected between post-natal day 0 (P0) and P7 and its level increased until P28 (Bernard (2010)). This high expression appears to come from up-regulation of Malat1 during differentiation, with in-vitro differentiation of neural stem cells showing significant up-regulation of expression in neuronal and glial differentiated progeny (Mercer (2010)).
Expressed in the nucleus accumbens of normal human brains and upregulated in this brain region in heroin abusers (Michelhaugh (2010)).
In neuroblastoma cells Malat1 was up-regulated by the hormone oxytocin (Koshimizu (2010)).
Malat1 is up-regulated in a range of cancers (Ji (2003), Yamada (2006), Lin (2007), Guffanti (2009)).
High expression of Malat1 is associated with metastasis in certain histological subtypes of non-small cell lung cancer (NSCLC) and is predictive of poor prognosis (Ji (2003)).
Malat1 is up-regulated in placenta previa increta/percreta, a disease characterised by excessive invasion of fetal placental trophoblasts into the uterus (Tseng (2009)).
Malat1 is stable in human B cells and Hela and wt MEFs (half-life >7 hrs) but has significantly lower stability in mouse 3T3 and N2A cells. Suggesting differences in Malat1 stability both within and between species (Friedel (2009), Bernard (2010), Clark (2012), Tani (2012)).
Malat1 localises to SC35 domain nuclear speckles in several cell lines (Hutchinson (2007)) (Clemson (2009)). Localisation to nuclear speckles is transcription-dependent, as RNA pol II inhibition promoted re-distribution of Malat1 ncRNA from nuclear speckles to a homogenous nuclear localisation (Bernard (2010)). Malat1 co-localises with pre-mRNA-splicing factor SF2/ASF and CC3 antigen in the nuclear speckles (Bernard (2010)).
MALAT1 is enriched in nuclear speckles in interphase cells and concentrates in mitotic interchromatin granule clusters (IGCs, structural analogs of nuclear speckles present in mitotic cells), but unlike Neat1 it is not required for the structural integrity of the nuclear domain (Tripathi (2010)).
mascRNA derived from Malat1 is transported to the cytoplasm (Wilusz (2008)).
|Function|| Summary: Malat1 has been found to regulate alternative splicing of endogenous target genes, and it is implicated in cancer and a series of molecular and cellular phenotypes, as indicated below.|
Identified as an oncogene that promotes tumorigensis. Expression of a Malat1 fragment in NIH 3T3 cells transformed cells (Li (2009)).
Knockdown inhibited cell mobility and lead to decreased expression of several genes (CTHRC1, CCT4, HMMR, or ROD1) that promoted cell migration (Tano (2010)). This result may also explain why knockdown inhibited trophoblast-like cell invasion in-vitro, with MALAT1 hypothesised to regulate the level of trophoblast invasion into the uterus in vivo (Tseng (2009)).
MALAT1 depletion resulted in aberrant mitosis, with a large fraction of cells accumulating at G2/M boundary, and increased cell death (Tripathi (2010)).
Depletion of Malat1 in neuroblastoma cells indicated that Malat1 affects the expression of genes involved not only in the organization and the function of the nucleus, but also in synapse function and dendrite development. In cultured hippocampal neurons, knock-down of Malat1 decreased synaptic density, whereas its over-expression resulted in a cell-autonomous increase in synaptogenesis (Bernard (2010)).
There is a significant enrichment for SRSF1 (SF2/ASF) binding sites within the 5' half of both human and mouse MALAT1, whose direct interaction has been demonstrated, and is dependent on its canonical RRM (RRM1) or the pseudo RRM (RRM2) domains (Sanford (2009), Tripathi (2010)). Independent sequence elements in MALAT1 influence its distribution to nuclear speckles and the recruitment of SRSF1 (Tripathi (2010)).
Additional interactions have been found between MALAT1 and SRSF1, SRSF2, and SRSF3 proteins, but only weak interactions with SRSF5 and PSP1 (an RNA-binding protein that is a component of paraspeckles) have been identified (Tripathi (2010)).
Knock-down of nuclear Malat1 in a transfected U2OS cell line showed that it modulates the recruitment of SR proteins (SRSF1 or SF2/ASF and SC35) to a transcriptionally active transgene array (stably integrated), indicating a role in the regulation of the association of pre-mRNA-splicing factors to transcription sites and control of post-transcriptional gene expression (Bernard (2010)). Malat1 modulates the speckle association of a subset of pre-mRNA splicing factors, such as SF1, U2AF-65, SF3a60, and B-U2snRNP (Tripathi (2010)).
Malat1-depleted HeLa cells show increased cellular levels of dephosphorylated SRSF1 (SF2/ASF) (Bernard (2010)), as well as a moderately increased cytoplasmic pool of poly(A)+ RNA (Tripathi (2010)). It has recently been shown to regulate alternative splicing of endogenous target genes by modulating SR splicing factor phosphorylation, affecting their levels and the distribution and ratio of phosphorylated to dephosphorylated pools (Tripathi (2010)).
Suggested to interact with the PRC2 complex in the HCT-116 cancer cell line (Guil (2012)).
|Conservation|| Therian mammals (found in oppossum as well as placental mammals) (Hutchinson (2007)).|
Recently described in zebrafish. Sequence homology to zebrafish was limited to the 3°Ø end, but the ~7kb long, single exon structure as well as positional synteny was conserved, as was the high expression in brain found identified in mammals (Ulitsky (2011)).
|Name|| Malat1: Metastasis-associated lung adenocarcinoma transcript 1.|
Neat2: Nuclear enriched abundant transcript 2
- Cite error: Invalid
<ref>tag; no text was provided for refs named
- Cite error: Invalid
<ref>tag; no text was provided for refs named