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SUMMARY:Tuning protein biogenesis at the level of translation: probing dim
 ensionality beyond the linear sequence of mRNA - Prof. Zoya Ignatova\, Ins
 titute of Biochem. & Mol. Biol.\, Univ. of Hamburg\, Germany
DTSTART:20181017T093000Z
DTEND:20181017T103000Z
UID:TALK109705@talks.cam.ac.uk
CONTACT:Tom Scheidt
DESCRIPTION:The ribosome is a central molecular machine that translates th
 e genetic information into a corresponding polypeptide in an mRNA template
 -directed manner. Thereby\, the mRNA is not a mere messenger for translati
 ng codons into amino acids. Emerging evidence places mRNA more centrally a
 s a direct effector of a variety of processes including translation effici
 ency\, co-translational folding\, assembly and cellular localization. We u
 se recent developments in deep sequencing technologies to probe translatio
 n on a global transcriptome-wide scale and show that mRNA bears additional
  layer of information that facilitates translation efficiency and is cruci
 al for co-translational folding and expression of the encoded protein. In 
 the context of these findings\, we present a new twist of the effect of sy
 nonymous and non-synonymous mutations. We find that the type of mutation\,
  i.e. whether along with the amino-acid exchanges it also alters translati
 on speed at a codon\, correlates with its effect on protein stability and 
 function and highlight the central role of translation in mediating the ef
 fect of mutations. Using one of the most polymorphic genes\, CFTR\, implic
 ated in cystic fibrosis pathology\, we show that such effects are likely t
 o influence the spectrum of disease symptoms\, represent a mechanistic con
 tributor to genotype-phenotype relationships\, and ultimately predict ther
 apeutic response in ‘precision’ theratyping studies.
LOCATION:Department of Chemistry\, Cambridge\, Unilever lecture theatre
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