Download Interference with ribosomal RNA production leads to the activation of

P029
Interference with ribosomal RNA production leads to the
activation of mTORC1 signaling, and translation initiation
and elongation factors
Rui Liu, Valentina Ladevaia, Ze Zhang and
Christopher G. Proud
University Of Southampton, Southampton, UK
Ribosome biogenesis occurs in the nucleolus and it is a complex,
highly-regulated process that involves the production of ribosomal
RNA by RNA polymerases I and III.Pol I generates a precursor
pre-rRNA which is processed to yield the 18S, 28S, and5.8S
rRNAs. The mammalian target of rapamycin complex (mTORC1)
promotes thetranscription and processing of rRNA and the translation of the mRNAs for ribosomalproteins (which are encoded by
5’-TOP mRNAs). Here we have studied the effectsof perturbing
the PeBoW complex, which comprises PES1, BOP1 and WDR12
and is required for processing the 28S rRNA.
Expressing a deletion mutant of BOP1, termed BOP1∆, impairs
PeBoW functionand 28S rRNA production. It also causes the
activation of mTORC1 signalling and the stimulation of proteins
that regulation the initiation and elongation stages of translation
(eIF4E and eEF2, respectively). In particular, BOP1∆ causes
thedephosphorylation of eEF2 due to the inhibition and downregulation of eEF2 kinase(eEF2K). Knocking down PeBoW
components has similar effects, as does inhibitingPol I with a low
dose of actinomycin D.
Our data demonstrate that disrupting rRNA production activates
mTORC1 signalling to enhance the efficiency of the existing
translational machinery, likely to help compensate for impaired
ribosome production.