TIA1

TIA1, or T-cell intracellular antigen 1, is an RNA-binding protein encoded by the human TIA1 gene. It belongs to the TIA1/TIAR family and participates in post-transcriptional gene regulation. TIA1 is expressed broadly and localizes to both the nucleus and cytoplasm; under cellular stress, it accumulates in cytoplasmic stress granules.

Structure and RNA binding: The protein features an N-terminal low-complexity, prion-like region that promotes self-assembly and stress-granule nucleation, followed by three RNA recognition motifs (RRM1-3) that bind U-rich RNA sequences. Through these domains, TIA1 regulates mRNA splicing, stability, and translational control of numerous transcripts.

Function: In normal conditions, TIA1 participates in the alternative splicing of a subset of pre-mRNAs and influences mRNA metabolism. During cellular stress, TIA1, along with TIAR and other stress-granule components, binds target mRNAs and represses translation by sequestering them in stress granules, aiding the cellular stress response.

Clinical significance: Mutations in TIA1 have been associated with neurodegenerative disease, including certain forms of amyotrophic lateral sclerosis and frontotemporal lobar degeneration, where altered phase separation and persistent stress granules may contribute to pathology. A notable pathogenic mutation is P362L in the prion-like domain, linked to disease in several studies.

See also: TIAR, stress granule, RNA-binding protein.