TIA1

Mammalian protein found in Homo sapiens

TIA1

Available structures

PDB

Ortholog search: PDBe RCSB

List of PDB id codes
2MJN, 3BS9

Identifiers

Aliases

TIA1, TIA-1, WDM, TIA1 cytotoxic granule-associated RNA binding protein, TIA1 cytotoxic granule associated RNA binding protein

External IDs

OMIM: 603518; MGI: 107914; HomoloGene: 20692; GeneCards: TIA1; OMA:TIA1 - orthologs

Gene location (Mouse)

Chr.	Chromosome 6 (mouse)^[1]

Band	6\|6 D1	Start	86,381,201 bp^[1]
Band	6\|6 D1	End	86,410,387 bp^[1]

Gene ontology
Molecular function	nucleic acid binding protein binding poly(A) binding RNA binding mRNA 3'-UTR AU-rich region binding
Cellular component	cytoplasm cytoplasmic stress granule nuclear stress granule nucleus nucleoplasm cytosol ribonucleoprotein complex
Biological process	negative regulation of translation positive regulation of epithelial cell apoptotic process regulation of mRNA splicing, via spliceosome protein localization to cytoplasmic stress granule apoptotic process fibroblast growth factor receptor signaling pathway
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


7072


21841

Ensembl


ENSG00000116001


ENSMUSG00000071337

UniProt


P31483


P52912

RefSeq (mRNA)


NM_022037 NM_022173


NM_001164078 NM_001164079 NM_011585

RefSeq (protein)

NP_071320 NP_071505 NP_001338437 NP_001338438 NP_001338439
NP_001338440 NP_001338441 NP_001338443 NP_001338444 NP_001338445 NP_001338446 NP_001338447 NP_001338448 NP_001338449 NP_001338450 NP_001338451 NP_001338452 NP_001338453 NP_001338454 NP_001338442


NP_001157550 NP_001157551 NP_035715

Location (UCSC)

n/a

Chr 6: 86.38 – 86.41 Mb

PubMed search

^[2]

^[3]

Wikidata

View/Edit Human

View/Edit Mouse

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.^[4] Under stress conditions, TIA1 localizes to cellular RNA-protein conglomerations called stress granules.^[5] It is encoded by the TIA1 gene.^[6]

Mutations in the TIA1 gene have been associated with amyotrophic lateral sclerosis, frontotemporal dementia, and Welander distal myopathy.^[7]^[8]^[9] It also plays a crucial role in the development of toxic oligomeric tau in Alzheimer's disease.^[10]

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.^[11] 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.^[11] 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.^[12] 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.^[13] 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.^[14] 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.

References

^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000071337 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Izquierdo JM, Majós N, Bonnal S, Martínez C, Castelo R, Guigó R, et al. (August 2005). "Regulation of Fas alternative splicing by antagonistic effects of TIA-1 and PTB on exon definition". Molecular Cell. 19 (4): 475–84. doi:10.1016/j.molcel.2005.06.015. PMID 16109372.
^ Kedersha NL, Gupta M, Li W, Miller I, Anderson P (December 1999). "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. doi:10.1083/jcb.147.7.1431. PMC 2174242. PMID 10613902.
^ "Entrez Gene: TIA1 cytotoxic granule-associated RNA binding protein".
^ Mackenzie IR, Nicholson AM, Sarkar M, Messing J, Purice MD, Pottier C, et al. (August 2017). "TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics". Neuron. 95 (4): 808–816.e9. doi:10.1016/j.neuron.2017.07.025. PMC 5576574. PMID 28817800.
^ Hackman P, Sarparanta J, Lehtinen S, Vihola A, Evilä A, Jonson PH, et al. (April 2013). "Welander distal myopathy is caused by a mutation in the RNA-binding protein TIA1". Annals of Neurology. 73 (4): 500–9. doi:10.1002/ana.23831. PMID 23401021. S2CID 13908127.
^ Klar J, Sobol M, Melberg A, Mäbert K, Ameur A, Johansson AC, et al. (April 2013). "Welander distal myopathy caused by an ancient founder mutation in TIA1 associated with perturbed splicing". Human Mutation. 34 (4): 572–7. doi:10.1002/humu.22282. PMID 23348830. S2CID 10955236.
^ Ash PE, Lei S, Shattuck J, Boudeau S, Carlomagno Y, Medalla M, et al. (March 2021). "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): e2014188118. doi:10.1073/pnas.2014188118. PMC 7936275. PMID 33619090.
^ ^a ^b Rayman JB, Kandel ER (May 2017). "TIA-1 Is a Functional Prion-Like Protein". Cold Spring Harbor Perspectives in Biology. 9 (5): a030718. doi:10.1101/cshperspect.a030718. PMC 5411700. PMID 28003185.
^ Anderson P, Kedersha N (March 2008). "Stress granules: the Tao of RNA triage". Trends in Biochemical Sciences. 33 (3): 141–50. doi:10.1016/j.tibs.2007.12.003. PMID 18291657.
^ Wolozin B, Ivanov P (November 2019). "Stress granules and neurodegeneration". Nature Reviews. Neuroscience. 20 (11): 649–666. doi:10.1038/s41583-019-0222-5. PMC 6986315. PMID 31582840.
^ Anderson P, Kedersha N, Ivanov P (July 2015). "Stress granules, P-bodies and cancer". Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1849 (7): 861–70. doi:10.1016/j.bbagrm.2014.11.009. PMC 4457708. PMID 25482014.