User:Robertsmclellan/sandbox



Final Article for Evaluation. I will move to mainspace next week

Note: secondary source is reference #4, all others are primary

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Function
MALAT1 forms a precursor transcript by cleaving a long non-coding RNA at its 3' end. This resulting mature RNA loses its polyadenylation signal and is instead capped at the 3' end by a triple helical structure. The nascent transcript is separated into two non coding RNAs that are functional within the nucleus. MALAT1 is highly expressed in many tissues of the body but is most active in the brain. Fluorescence in-situ hybridization has shown mature transcripts in the pyramidal neurons located in the hippocampal region, Purkinje cells in the cerebellum, and neurons located in the substantia nigra. Specifically, it is expressed in Purkinje cells during the first few weeks of post-natal development, playing an essential role in cell differentiation. In addition, MALAT1 is associated with cell cycle regulation. It associates with nuclear speckles during interphase and forms mitotic granule clusters to support the nucleus during cell division. These clusters form scaffolds for ribonucleoprotein complexes to initiate further signalling events in the cell.

Lung cancer
MALAT1 has been widely studied for its association with cancer in humans, thus labeled an oncogene. Lung cancer is of particular interest because MALAT1 upregulation is linked to metastasis and cell migration. MALAT1 activates cell migration by controlling transcriptional and post-transcriptional regulation of genes that are associated with cell migration. Collagen triple helix repeat containing 1 (CTHRC1), chaperonin-containing tailless complex polypeptide, subunit 4 (CCT4), hyaluronan-mediated motility receptor (HMMR) and regulator of differentiation 1 (ROD1) are genes observed to be over-expressed in human lung cancer tissues. MALAT1 recruits splice factor proteins, demonstrating its role in regulating how splice factor proteins associate with transcription sites and thus controlling expression of these four genes. This process is generally poorly understood, although over-expression of MALAT1 observed in cancer is believed be associated with over-expression of CTHRC1, CCT4, HMMR, and ROD1.

Neuroblastoma
Knock-out of MALAT1 in neuroblastoma cells demonstrates it plays a role in the expression of genes associated with synaptic signalling, formation of dendrites, and propagation of electrical impulses. MALAT1 has additional functions to nucleus organization and signal transduction. In hippocampal regions, knock-out of MALAT1 lowered neuronal synaptic density; however its upregulation yielded a cellular increase in synaptogenesis.

Heroin addiction
Over-expression of MALAT1 has been observed in the nucleus accumbens of heroin addicts compared to drug-free control subjects. Abnormal function of long non-coding mRNAs like MALAT1 are proposed to be modulators of genome-wide changes that occur during drug abuse.