1) the gene was then renamed cold shock domain containing E1 ( CSDE1). Later it was discovered that UNR encodes a protein possessing 5 cold shock domains, which undergoes alternative splicing (see Fig. This gene was initially identified as a regulator of N-Ras expression. The final member of this family is denoted upstream of N-RAS ( UNR). PIPPin is found with ribonucleoprotein complexes, where it interacts with other RNA binding proteins, e.g.
PIPPin expression is restricted to brain, where it binds mRNA to regulate translation. CARHSP1 binds to and stabilizes tumor necrosis factor (TNF) mRNA within P-bodies and exosomes. Originally identified as a substrate of the calcium/calmodulin-regulated protein phosphatase calcineurin, CARHSP1 is a paralog of the brain-specific cold shock protein PIPPin. Ī further member of the human cold shock protein family is the calcium-regulated heat-stable protein 1 (CARHSP1) a 24 kDa protein also known as CRHSP-24. In addition to miRNAs, Lin28 also binds to mRNAs, participating in a number of ribonucleoprotein complexes, such as P-bodies and stress granules, to regulate translation. let-7 also targets Lin28 creating a double-negative feedback loop. Of particular note is the ability of Lin28 to repress let-7 miRNAs, e.g. In addition to the cold shock domain, Lin28A/B are unique in that they also possess two CCHC type zinc fingers, which form a knuckle domain that also participates in nucleic acid binding. However, it was its potential for cellular reprogramming that brought it into the spotlight, as together with Oct3, Sox2, and Nanog, Lin28 is able to revert differentiated cells into their pluripotent state. Īnother developmentally important cold shock protein expressed in humans is Lin28, which was first characterized as a developmental factor in C. The Ybx3 knockout is viable, however the Ybx1/Ybx3 double knockout shows a more severe developmental phenotype indicating overlapping activities during development. The Ybx1 knockout mouse is embryonic lethal indicating an important role during development. In humans, two isoforms of DbpA are reported (DbpA_a and DbpA_b), which differ by an alternatively spliced exon that encodes the 69 amino acid long unique domain located adjacent to the CSD. However, following birth the expression of Ybx3 (DbpA) is down-regulated in most tissues, the exceptions being heart, skeletal muscle, blood vessels, and testis. Whereas Ybx2 expression is restricted to germ cells, Ybx1 and Ybx3 are ubiquitously expressed during development. Two additional family members exist, DNA binding protein A (DbpA) and C (DbpC), which are encoded by the genes YBX3 and YBX2, respectively. The prototypic member is Y-box binding protein-1 (YB-1), also known as DNA binding protein B (DbpB), encoded by the gene YBX1.
In humans, the predominant group of cold shock domain proteins is denoted the Y-box protein family. RNase R appears to be responsible for degrading misfolded RNAs, while CspA melts double-stranded RNAs to enable translation. The authors identified RNase R and CspA to be the major players. A recent study revisited the original observation using genome-wide methods to analyze the global changes occurring in bacteria during the cold shock response. This rapid inducibility is conserved amongst species. Cold shock proteins were initially identified in bacteria, where a sudden drop in temperature (from 37 ☌ to 10 ☌) induced a 200-fold increase in cold shock protein A (CspA) expression within minutes, which was independent of transcriptional activity.
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