Heterogeneous nuclear ribonucleoproteins (hnRNPs), which directly bind to nascent RNA polymerase II transcripts, play an important role in both transcript-specific packaging and alternative splicing of pre-mRNAs. These "M proteins" are pre-mRNA-binding proteins in vivo, and they bind to poly(G) and poly(U) RNA homopolymers in vitro. hnRNP-M4 is the largest M protein, with 729 amino acids and a molecular mass of about 77 kD. The M4 protein contains 3 ribonucleoprotein consensus sequence RNA-binding domains of approximately 90 amino acids each, a glycine- and methionine-rich region, and an MR (methionine/arginine) repeat motif. It also contains 9 potential casein kinase type II phosphorylation sites and a tyrosine phosphorylation site. Two-dimensional gels showed multiple M4 isoforms, which may be the result of phosphorylation. This antibody also recognizes hnRNP-M3 as well.
