Home  About us  Contact
 

RNA Decay (rna + decay)

Distribution by Scientific Domains
Life Sciences100%

Selected Abstracts

Consequences of RNase E scarcity in Escherichia coli

MOLECULAR MICROBIOLOGY, Issue 4 2002
Chaitanya Jain
Summary The endoribonuclease RNase E plays an important role in RNA processing and degradation in Escherichia coli. The construction of an E. coli strain in which the cellular concentration of RNase E can be precisely controlled has made it possible to examine and quantify the effect of RNase E scarcity on RNA decay, gene regulation and cell growth. These studies show that RNase E participates in a step in the degradation of its RNA substrates that is partially or fully rate-determining. Our data also indicate that E. coli growth requires a cellular RNase E concentration at least 10,20% of normal and that the feedback mecha-nism that limits overproduction of RNase E is also able to increase its synthesis when its concentration drops below normal. The magnitude of the in-crease in RNA longevity under conditions of RNase E scarcity may be limited by an alternative pathway for RNA degradation. Additional experiments show that RNase E is a stable protein in E. coli. No other E. coli gene product, when either mutated or cloned on a multicopy plasmid, seems to be capable of compensating for an inadequate supply of this essential protein. [source]

Drug-induced readthrough of premature stop codons leads to the stabilization of laminin ,2 chain mRNA in CMD myotubes

THE JOURNAL OF GENE MEDICINE, Issue 2 2008
Valérie Allamand
Abstract Background The most common form of congenital muscular dystrophy is caused by a deficiency in the ,2 chain of laminin-211, a protein of the extracellular matrix. A wide variety of mutations, including 20 to 30% of nonsense mutations, have been identified in the corresponding gene, LAMA2. A promising approach for the treatment of genetic disorders due to premature termination codons (PTCs) is the use of drugs to force stop codon readthrough. Methods Here, we analyzed the effects of two compounds on a PTC in the LAMA2 gene that targets the mRNA to nonsense-mediated RNA decay, in vitro using a dual reporter assay, as well as ex vivo in patient-derived myotubes. Results We first showed that both gentamicin and negamycin promote significant readthrough of this PTC. We then demonstrated that the mutant mRNAs were strongly stabilized in patient-derived myotubes after administration of negamycin, but not gentamicin. Nevertheless, neither treatment allowed re-expression of the laminin ,2-chain protein, pointing to problems that may have arisen at the translational or post-translational levels. Conclusions Taken together, our results emphasize that achievement of a clinical benefit upon treatment with novel readthrough-inducing agents would require several favourable conditions including PTC nucleotide context, intrinsic and induced stability of mRNA and correct synthesis of a full-length active protein. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Nonsense-mediated RNA decay: A molecular system micromanaging individual gene activities and suppressing genomic noise

BIOESSAYS, Issue 5 2005
Claudio R. Alonso
Nonsense-mediated RNA decay (NMD) is an evolutionary conserved system of RNA surveillance that detects and degrades RNA transcripts containing nonsense mutations. Given that these mutations arise at a relatively low frequency, are there any as yet unknown substrates of NMD in a wild-type cell? With this question in mind, Mendell et al.1 have used a microarray assay to identify those human genes under NMD regulation. Their results show that, in human cells, NMD regulates hundreds of physiologic transcripts and not just those containing nonsense mutations. Among the NMD targets are a number of non-functional RNAs expressed from vestigial sequences derived from retroviral and transposable elements. These findings support the notion that NMD is a high profile post-transcriptional mechanism micromanaging the activity of multiple gene batteries and suppressing the expression of genetic remnants. BioEssays 27:463,466, 2005. © 2005 Wiley Periodicals, Inc. [source]