TIA1 or Tia1 cytotoxic granule-associated rna binding protein is a 3'UTR
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the ...
binding protein that can bind the 5'TOP sequence of 5'TOP mRNAs. It is associated with programmed cell death (
apoptosis) and regulates
alternative splicing of the gene encoding the
Fas receptor
The Fas receptor, also known as Fas, FasR, apoptosis antigen 1 (APO-1 or APT), cluster of differentiation 95 (CD95) or tumor necrosis factor receptor superfamily member 6 (TNFRSF6), is a protein that in humans is encoded by the ''FAS'' gene. Fas ...
, an apoptosis-promoting protein.
Under stress conditions, TIA1 localizes to cellular RNA-protein conglomerations called
stress granules. It is encoded by the TIA1
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Mutations in the ''TIA1'' gene have been associated with
amyotrophic lateral sclerosis,
frontotemporal dementia, and Welander
distal myopathy. It also plays a crucial role in the development of toxic oligomeric tau in
Alzheimer's disease.
Function
This protein is a member of a RNA-binding protein family that regulates
transcription
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
and
RNA translation. It was first identified in cytotoxic lymphocyte (CTL) target cells. TIA1 acts in the nucleus to regulate splicing and transcription.
TIA1 helps to recruit the splicesome to regulate RNA splicing, and it inhibits transcription of multiple genes, such as the cytokine
Tumor necrosis factor alpha
Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolo ...
.
In response to stress, TIA1 translocates from the nucleus to the cytoplasm, where it nucleates a type of RNA granule, termed the
stress granule, and participates in the translational stress response. As part of the translational stress response, TIA1 works in cooperation with other RNA binding proteins to sequester RNA transcripts away from the ribosome, which allows the cell to focus its protein synthesis/RNA translation machinery on producing proteins that will address the particular stress. It has been suggested that this protein may be involved in the induction of apoptosis as it preferentially recognizes poly(A) homopolymers and induces DNA fragmentation in CTL targets.
The major granule-associated species is a 15-kDa protein that is thought to be derived from the carboxyl terminus of the 40-kDa product by proteolytic processing. Alternative splicing resulting in different isoforms of this gene product have been described.
See also
*
Stress granule
*
T-cell large granular lymphocyte leukemia
References
Further reading
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External links
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