TIS11B is an RNA-binding protein encoded by the ZFP36L1 gene, which is widely expressed across human tissues and cell types. TIS11B was found to form TIS granules through physiological assembly. TIS11B generates reticular assemblies that are intertwined with the peri-nuclear ER and that enrichs specific mRNAs and proteins. The association between TIS granules and the ER creates a subcellular compartment—the TIGER domain (TIS granule-ER)—with a biophysically and biochemically distinct environment from the cytoplasm. TIS granules enable translation of mRNAs with AU-rich elements at an ER subdomain. Specific protein-protein interactions can only be formed in the TIS granule region. mRNAs that combine the presence of multiple AREs in their 3'UTRs and the presence of at least one region that encodes a transmembrane domain, are enriched in TIS granules, whereas in the absence of both features mRNAs are excluded from TIS granules. TIS11B assemblies are called TIS granules as they enrich LU mRNA, because they have the characteristics of RNA granules. TIGER compartment promotes 3'UTR-mediated interaction of SET with membrane proteins, thus allowing increased surface expression and functional diversity of proteins, including CD47 and PD-L1. It has been shown that TIS11B assembly is not caused by the presence of the IDR, but instead is charge pattern driven. Importantly, regulation of mRNA stability can be accomplished by soluble TIS11B, but TIS11B assembly is required for the collective properties of the protein that endow it with the ability to regulate protein functions through mediating 3'UTR-dependent protein-protein interactions. TIS11B assembly is conserved among vertebrate species. However, no in vitro investigation of the protein were performed. As a conclusion, the association of TIS granules with the ER creates a subcellular compartment with special properties that is necessary and sufficient for SET transfer from mRNAs to proteins, and thus, for the 3'UTR-dependent interaction of SET, and likely other proteins, with membrane proteins (PMID:30449617)
Literature supporting the
LLPS: 30449617
Functional class of membraneless organelle:
activation/nucleation/signal amplification/bioreactor; biomolecular filter/selectivity barrier