Abstract
It has recently become clear that the misassembly of ribosomes in eukaryotic cells can have deleterious effects that go far beyond a simple shortage of ribosomes. In this work we find that cells deficient in ribosomal protein L1 (Rpl1; Rpl10a in mammals) produce ribosomes lacking Rpl1 that are exported to the cytoplasm and that can be incorporated into polyribosomes. The presence of such defective ribosomes leads to slow growth and appears to render the cells hypersensitive to lesions in the ubiquitin-proteasome system. Several genes that were reasonable candidates for degradation of 60S subunits lacking Rpl1 fail to do so, suggesting that key players in the surveillance of ribosomal subunits remain to be found. Interestingly, in spite of rendering the cells hypersensitive to the proteasome inhibitor MG132, shortage of Rpl1 partially suppresses the stress-invoked temporary repression of ribosome synthesis caused by MG132.
Highlights
IntroductionIn a growing cell it utilizes a very substantial fraction of the cell’s resources [1]
The synthesis of ribosomes is a special challenge to the cell in two respects
Subunits lacking L1 can be found in polysomes For a more thorough analysis of the synthesis of 60S ribosomal subunits in the absence of ribosomal protein L1 (Rpl1), we developed a strain in which the synthesis of Rpl1 could be completely repressed along with control strains to repress synthesis of Rpl4 or Rps6
Summary
In a growing cell it utilizes a very substantial fraction of the cell’s resources [1]. Perhaps more importantly, it requires the coordinated production of each of the 79 ribosomal proteins (RPs), which are needed, with a couple of exceptions, in exactly equimolar amounts. There is substantial evidence from both yeast and metazoan systems that an imbalance of RPs can lead to stress, often termed ‘nucleolar stress’ (reviewed in [2],[3]). In humans haploinsufficiency for any of several RPs leads to DiamondBlackfan anemia and associated pathology, including increased incidence of cancer [9]. The role of ribosomopathies in human disease is only just beginning to be appreciated
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call