The Multifunctional Faces of T-Cell Intracellular Antigen 1 in Health and Disease

Abstract

T-cell intracellular antigen 1 (TIA1) is an RNA-binding protein that is expressed in many tissues and in the vast majority of species, although it was first discovered as a component of human cytotoxic T lymphocytes. TIA1 has a dual localization in the nucleus and cytoplasm, where it plays an important role as a regulator of gene-expression flux. As a multifunctional master modulator, TIA1 controls biological processes relevant to the physiological functioning of the organism and the development and/or progression of several human pathologies. This review summarizes our current knowledge of the molecular aspects and cellular processes involving TIA1, with relevance for human pathophysiology.

Bibliometric Overview on T-Cell Intracellular Antigens and Their Pathological Implications

“…In addition, keywords related to cytotoxicity, T-lymphocytes, viral infections (including Epstein–Barr Virus/herpesvirus 4) and immune response mechanisms are shared in the cluster, highlighting their importance in immune-related functions and surveillance and viral pathways. Collectively, these findings demonstrate that both proteins contribute to the regulation of cytotoxic T-lymphocytes, which are critical for immune responses against viruses and cancers [ 4 , 6 , 36 ], including lymphoma.…”

“…Although both proteins are widely expressed in human tissues, their distribution differs. TIA1 is highly expressed in the kidney and gonads, with significant expression in the small intestine, lung, skeletal muscle and pancreas [ 4 ], whereas TIAR is predominantly expressed in the brain and skeletal muscle, with lower expression in the heart, kidney and lung [ 6 ].…”

T-Cell Intracellular Antigen 1-Like Protein in Physiology and Pathology

“…However, as in the case of TIA1, precise information on the intimate structural details as well as methodology to address the experimental challenges represented by the structural “Pandora’s box” located in the carboxyl-terminal disorganized region (IDR) is lacking. Likely, the development of new methodologies and algorithms will help to unravel its grammar and language within the proteomic universe of networks, and elucidate its functional dynamics [ 8 ].…”

“…Nonetheless, an oncogenic or tumor suppressor function for TIAR (and their isoforms) could be highly dependent on the cell-type and the associated interactomes involving both RNA-protein and protein–protein interactions and dynamics [ 8 , 21 ]. TIAR ablation in murine embryonic fibroblasts compromises cell proliferation by delaying cell cycle at G2/M phase and triggering adaptive autophagy [ 93 ].…”

“…At the amino acid level, TIAR and TIA1 share 85% homology in the amino-terminal region; specifically, RRM1–3 share 79%, 92% and 91% homology, respectively, and the C-terminal region shares 51% homology ( Figure 3 ). As well as having structural similarities, TIAR, as a TIA1 paralog and vice versa, has overlapping functions with TIA1 in the field of gene expression, cellular events and pathophysiology, for instance, because they regulate specific and overlapping aspects of the transcriptome, translatome and interactome (RNA and/or protein complexes), suggesting that their functional effects can be redundant, additive and even independent [ 8 ], as we will see below.…”