Kawahara et al. reveal how a translation-blocking protein performs its job. The protein makes a nuisance of itself, getting in the way of another protein that is essential for starting translation.
The researchers had previously discovered that the protein, Musashi-1, prevents neural stem cells from differentiating by stalling translation of mRNA for m-Numb, which helps orchestrate cell specialization. But how Musashi-1 halts translation was a mystery. Other translation-blocking proteins thwart the initial step of the process by which the small ribosomal subunit latches onto a newly minted mRNA strand. Two vital proteins for completing this step are the eukaryotic initiation factor eIF4G and the poly (A) binding protein (PABP). They connect and help bring the small ribosomal subunit into position.
Kawahara et al. showed that Musashi-1 also hooks up with PABP. A mutant Musashi-1 lacking the PABP-recognizing sequence could not attach to PABP or halt translation. The team also found that Musashi-1 competed with eIF4G to bind to PABP.
To determine whether this competition hampers translation, the researchers measured how well ribosomes bound to mRNA in Musashi-1's presence. The small ribosomal subunit settled onto the mRNA just fine. However, Musashi-1 hampered the attachment of the large ribosomal subunit, which is also necessary to make a functional ribosomal complex. Because a variety of stem cells make Musashi-1, it might be a key factor for controlling stem cell differentiation, according to the researchers.