Thursday, July 5, 2012

More fun with fun12... right, that was a dreadful joke

I like translational GTPases. I particularly like bacterial ones. Hell, I am titrating one with GTP as we speak, so I am partial. However, eukaryotic translational GTPases are also OK, particularly the ones that have bacterial homologues.

One of these is eukaryotic initiation factor 5B, eIF5B, a homologue of bacterial initiation factor 2, IF2. In S. cerevisiae eIF5B is called Fun12. eIF5B is a GTPase, and translational GTPases are tightly regulated. During translation initiation Fun12 is involved in the subunit joining, and GTP hydrolysis is coupled with factor's release from the initiation complex

Now it turnes out that Fin12/eIF5B has another function outside of translation initiation: together with the 60S subunit it proofreads the ribosomal assembly (Lebaron et al. 2012 and Strunk et al. 2012). Assembly of the ribosomal subunits is a multistep process, with r-proteins binding is certain sequence, assisted by various assembly factors, with rRNA being cut and remodeled. One of the steps is cleavage of the 18S rRNA by the Nob1 RNAse. And this stage, apparently, is stimulated by Fun12. Bacterial Fun12 homologue, IF2, is GTP-dependently rearranging the ribosomal structure by inducing intersubunit rotation, so the same process is now suggested to play the role in 40S maturation in yeast via driving the ribosome in Nob1-susceptible state.

In eucaryotes translation-incompetent ribosomes undergo so-called nonfunctional rRNA decay, NRD. By linking functionality on Fun12 binding and activation via consecutive 60S binding, translational functionality is linked to rRNA processing, providing another safety net making sure that only functional ribosomes are involved in translation, and the nonfunctional ones are rapidly cleared out.


Lebaron et al. Proofreading of pre-40S ribosome maturation by a translation initiation factor and 60S subunits. Nature Str. Mol. Biol. 2012 in press PIMD: 22751017

Strunk et al. A Translation-Like Cycle Is a Quality Control Checkpoint for Maturing 40S Ribosome Subunits. Cell 2012 vol. 150 (1) pp. 111-121 PIMD: 22770215

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