By
screening a human phytohemagglutinin-activated T-cell cDNA library with a TIA1
cDNA, Kawakami et al. (1992) cloned a cDNA encoding TIA1-related protein (TIAR). Both
TIAR and TIA1 are members of a family of RNA-binding proteins containing 3 RNA-binding
domains and a C-terminal auxiliary domain. Like TIA1, TIAR possesses a lysosome-targeting
motif in its C-terminal auxiliary domain, suggesting that TIAR is also a cytotoxic
granule-associated protein. The authors demonstrated that TIAR binds specifically to poly(A)
homopolymers, fragments DNA in permeabilized target cells, and is expressed in a wide variety of
hematopoietic and nonhematopoietic cell types.
NCBI Summary:
The protein encoded by this gene is a member of a family of RNA-binding proteins, has three RNA recognition motifs (RRMs), and binds adenine and uridine-rich elements in mRNA and pre-mRNAs of a wide range of genes. It regulates various activities including translational control, splicing and apoptosis. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. The different isoforms have been show to function differently with respect to post-transcriptional silencing. [provided by RefSeq, Jul 2008]
General function
Cell proliferation
Comment
Cellular localization
Cytoplasmic
Comment
candidate123
Ovarian function
Germ cell development, Germ cell migration
Comment
Expression regulated by
Comment
Ovarian localization
Comment
A primate perspective on oocytes and transgenerational PCOS. Dumesic DA et al. (2020) 'Androgenized' rodent models are widely used to explore the pathophysiology underlying human polycystic ovary syndrome (PCOS), including reproductive and metabolic dysfunction. Based on a recent study using a dihydrotestosterone (DHT)-treated murine model, it has been proposed that prenatal androgen excess alone can predispose to transgenerational transmission of PCOS. From RNA sequencing analysis of metaphase II (MII) oocytes of androgenized lineages, the authors speculated that oocyte factors, including up-regulation of cytotoxic granulosa-associated RNA binding protein-like 1 (TiaL1), are sufficient to promote disease transfer across generations. Although this is an intriguing concept, it was not considered in the context of earlier publications in which the transcriptomes of human MII oocytes from PCOS women undergoing IVF were compared with women without PCOS. In one of these papers, a number of differentially expressed genes in PCOS MII oocytes (TIAL1 was not differentially expressed) were found to have putative response elements in their promoters for androgen receptors and peroxisome proliferating receptor gamma, providing a mechanism for how excess androgens and/or metabolic defects associated with PCOS might affect female germ cells.//////////////////
Follicle stages
Comment
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
2 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: infertile - ovarian defect Comment:Beck AR et al 1998 reported that RNA-binding protein TIAR is essential for primordial germ cell
development.
Primordial germ cells (PGCs) give rise to both eggs and sperm via complex
maturational processes that require both cell migration and proliferation.
However, little is known about the genes controlling gamete formation during the
early stages of PGC development. The authors report
that mutant mice lacking TIAR, an RNA recognition motif/ribonucleoprotein-type
RNA-binding protein highly expressed in PGCs, fail to develop spermatogonia or
oogonia. This developmental defect is a consequence of reduced survival of
PGCs that migrate to the genital ridge around embryonic day 11.5 (E11.5). The
numbers of PGCs populating the genital ridge in TIAR-deficient embryos are
severely reduced compared to wild-type embryos by E11.5 and in the mutants
PGCs are completely absent at E13.5. Furthermore, TIAR-deficient embryonic
stem cells do not proliferate in the absence of exogenous leukemia inhibitory
factor in an in vitro methylcellulose culture assay, supporting a role for TIAR in
regulating cell proliferation. Because the development of PGCs relies on the
action of several growth factors, these results are consistent with a role for TIAR
in the expression of a survival factor or survival factor receptor that is essential
for PGC development. TIAR-deficient mice thus provide a model system to study
molecular mechanisms of PGC development and possibly the basis for some
forms of idiopathic infertility.
Species: human
Mutation name: type: naturally occurring fertility: subfertile Comment: Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome. Risal S et al. (2019) How obesity and elevated androgen levels in women with polycystic ovary syndrome (PCOS) affect their offspring is unclear. In a Swedish nationwide register-based cohort and a clinical case-control study from Chile, we found that daughters of mothers with PCOS were more likely to be diagnosed with PCOS. Furthermore, female mice (F0) with PCOS-like traits induced by late-gestation injection of dihydrotestosterone, with and without obesity, produced female F1-F3 offspring with PCOS-like reproductive and metabolic phenotypes. Sequencing of single metaphase II oocytes from F1-F3 offspring revealed common and unique altered gene expression across all generations. Notably, four genes were also differentially expressed in serum samples from daughters in the case-control study and unrelated women with PCOS. Our findings provide evidence of transgenerational effects in female offspring of mothers with PCOS and identify possible candidate genes for the prediction of a PCOS phenotype in future generations. expression of TIAL1 was significantly upregulated in the serum of women with PCOS (unrelated and daughters), in the adipose tissue of women with PCOS28 and in the MII oocytes of the androgenized lineage.//////////////////