TIA1 explained

TIA1 or Tia1 cytotoxic granule-associated rna binding protein is a 3'UTR mRNA 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, an apoptosis-promoting protein.[1] Under stress conditions, TIA1 localizes to cellular RNA-protein conglomerations called stress granules.[2] It is encoded by the TIA1 gene.[3]

Mutations in the TIA1 gene have been associated with amyotrophic lateral sclerosis, frontotemporal dementia, and Welander distal myopathy.[4] [5] [6] It also plays a crucial role in the development of toxic oligomeric tau in Alzheimer's disease.[7]

Function

This protein is a member of a RNA-binding protein family that regulates transcription and RNA translation. It was first identified in cytotoxic lymphocyte (CTL) target cells. TIA1 acts in the nucleus to regulate splicing and transcription.[8] 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. 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.[9] 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.[10] 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.[11] 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

Further reading

Notes and References

  1. Izquierdo JM, Majós N, Bonnal S, Martínez C, Castelo R, Guigó R, Bilbao D, Valcárcel J . 6 . Regulation of Fas alternative splicing by antagonistic effects of TIA-1 and PTB on exon definition . Molecular Cell . 19 . 4 . 475–84 . August 2005 . 16109372 . 10.1016/j.molcel.2005.06.015 . free .
  2. Kedersha NL, Gupta M, Li W, Miller I, Anderson P . RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2 alpha to the assembly of mammalian stress granules . The Journal of Cell Biology . 147 . 7 . 1431–42 . December 1999 . 10613902 . 2174242 . 10.1083/jcb.147.7.1431 .
  3. Web site: Entrez Gene: TIA1 cytotoxic granule-associated RNA binding protein .
  4. Mackenzie IR, Nicholson AM, Sarkar M, Messing J, Purice MD, Pottier C, Annu K, Baker M, Perkerson RB, Kurti A, Matchett BJ, Mittag T, Temirov J, Hsiung GR, Krieger C, Murray ME, Kato M, Fryer JD, Petrucelli L, Zinman L, Weintraub S, Mesulam M, Keith J, Zivkovic SA, Hirsch-Reinshagen V, Roos RP, Züchner S, Graff-Radford NR, Petersen RC, Caselli RJ, Wszolek ZK, Finger E, Lippa C, Lacomis D, Stewart H, Dickson DW, Kim HJ, Rogaeva E, Bigio E, Boylan KB, Taylor JP, Rademakers R . 6 . TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics . Neuron . 95 . 4 . 808–816.e9 . August 2017 . 28817800 . 5576574 . 10.1016/j.neuron.2017.07.025 .
  5. Hackman P, Sarparanta J, Lehtinen S, Vihola A, Evilä A, Jonson PH, Luque H, Kere J, Screen M, Chinnery PF, Åhlberg G, Edström L, Udd B . 6 . Welander distal myopathy is caused by a mutation in the RNA-binding protein TIA1 . Annals of Neurology . 73 . 4 . 500–9 . April 2013 . 23401021 . 10.1002/ana.23831 . 13908127 .
  6. Klar J, Sobol M, Melberg A, Mäbert K, Ameur A, Johansson AC, Feuk L, Entesarian M, Orlén H, Casar-Borota O, Dahl N . 6 . Welander distal myopathy caused by an ancient founder mutation in TIA1 associated with perturbed splicing . Human Mutation . 34 . 4 . 572–7 . April 2013 . 23348830 . 10.1002/humu.22282 . 10955236 .
  7. Ash PE, Lei S, Shattuck J, Boudeau S, Carlomagno Y, Medalla M, Mashimo BL, Socorro G, Al-Mohanna LF, Jiang L, Öztürk MM, Knobel M, Ivanov P, Petrucelli L, Wegmann S, Kanaan NM, Wolozin B . 6 . TIA1 potentiates tau phase separation and promotes generation of toxic oligomeric tau . Proceedings of the National Academy of Sciences of the United States of America . 118 . 9 . March 2021 . e2014188118 . 33619090 . 7936275 . 10.1073/pnas.2014188118 . free .
  8. Rayman JB, Kandel ER . TIA-1 Is a Functional Prion-Like Protein . Cold Spring Harbor Perspectives in Biology . 9 . 5 . a030718 . May 2017 . 28003185 . 5411700 . 10.1101/cshperspect.a030718 .
  9. Anderson P, Kedersha N . Stress granules: the Tao of RNA triage . Trends in Biochemical Sciences . 33 . 3 . 141–50 . March 2008 . 18291657 . 10.1016/j.tibs.2007.12.003 .
  10. Wolozin B, Ivanov P . Stress granules and neurodegeneration . Nature Reviews. Neuroscience . 20 . 11 . 649–666 . November 2019 . 31582840 . 6986315 . 10.1038/s41583-019-0222-5 .
  11. Anderson P, Kedersha N, Ivanov P . Stress granules, P-bodies and cancer . Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms . 1849 . 7 . 861–70 . July 2015 . 25482014 . 4457708 . 10.1016/j.bbagrm.2014.11.009 .

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