Regulation and role of an RNA-binding protein Msa2 in controlling the sexual differentiation of fission yeast

The msa2/nrd1 gene encodes an RNA-binding protein that negatively regulates sexual differentiation of fission yeast Schizosaccharomyces pombe by repressing the Ste11-regulated genes. However, it is not known how Msa2 regulates sexual differentiation, and to characterize its role, we altered the msa2 gene by inducing point mutations and tested the resulting mutants for their ability to inhibit sexual differentiation and their suppressive effect on a temperature sensitive pat1 mutant. Several amino acids were found to be important, including three phenylalanine residues (F153, F245 and F453) in the three consensus RNA recognition motifs (RRMs) and a threonine residue (T126) that normally functions as a phosphorylation site. Results indicated that Msa2 was negatively regulated by phosphorylation that arose from Spk1-mediated pheromone signaling. Msa2 also regulated the Ste11 protein level coordinating with Cpc2, a ribosomal-associated protein. In addition, Msa2 was detected in stress granules that co-localized with Pabp in the cytosol under conditions of glucose starvation. Msa2 may regulate the translation of Ste11, be a component of stress granules that form in response to glucose starvation, and regulate the sexual differentiation of S. pombe.