transcript targetting.

[ebarak at NSF.GOV]

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THis is in response to a posting by Derek.  My understanding of the current
understanding of protein targeting is that specificity is mediated entirely
by protein (rather than mRNA) sequences.  In other words, the localization of a
 protein is governed by the presence/absence of a signal sequence/mitochondrial
 localization/vacuolar/chloroplast/etc. and that there is a single biochemical
class of cytoplasmic ribosomes.  Am I wrong?  If I am wrong, what is the eviden
ce that suggests I am wrong?  Is there clear evidence that untranslated mRNA
sequences are actually involved in protein localization?  What is this evidence
?


          *************  REPLY: *********

I am sorry, but you are wrong.  You are limiting your thoughts to the 
problem of proteins getting associated with and/or across membrane 
barriers.  In such instances, the "targetting" information is in the 
amino acid sequence of signal peptides of one sort or another.  
However, there is also the very important biological problem of 
getting cytoplasmic proteins to specific non-membrane-bounded 
cytoplasmic regions.

 There is mounting evidence from a number of laboratories that certain 
mRNA sequences themselves have targetting information; that these 
specific mRNAs are (by as-yet unknown mechanisms) translocated to 
specific regions of the cytoplasm, where they are locally translated 
(by plain old ordinary cytoplasmic ribosomes).  This phenomenon is of 
particular relevance to embryonic development and pattern formation, 
but may also be of significance for normal morphogenesis and 
functioning of highly differentiated cell types.

For references, I would refer you as a start to several presentations 
made at the American Society for Cell Biology Annual meeting in New 
Orleans this past December (the abstracts are published in the Oct. 
1993 supplement to Molecular Biology of the Cell).  There was a major 
symposium talk by Ruth Lehmann (Whitehead Institute, MIT) on RNA and 
Protein Localization Within the Drosophila Oocyte (no published 
abstract, unfortunately!), and a "minisymposium" on mRNA localization 
chaired by Mary Lou King (University of Miami Medical School) 
featuring talks from Bruce Alberts' laboratory (W.E. Theurkauf et al., 
on the role of the cytoskeleton in mediating how specific mRNA species 
accumulate asymmetrically in Drosophila oocytes), Lipshitz et al (Cal 
Tech) on localization of maternal RNAs during Drosophila oogenesis and 
enbryogenesis, MacDonald et al, (Stanford U.) on mRNA localization 
during Drosophila oogenesis, R.H. Singer's lab ((Kislauskis et al., 
from U. Mass <\MEd. School) on sequences required for intracellular 
localization of beta-actin mRNA, G. Banker's lab (O. Steward et al., 
U. Va. Med .School) on  intracellular transport of RNA in neurons, and 
from Mary Lou King's own lab on RNA localization to the vegetal cortex 
of Xenopus oocytes.  Workers in this area of study have already begun 
to do the obvious "domain-swapping" experiments and are beginning to 
develop a small but growing library of which mRNA targetting sequences 
lead to which subcellular localizations.  

Other workers in this general area of study, besides the labs listed 
above, include William Jeffery's (Bodega Marine Lab, Univ. of 
California) and Alice Fulton's (University of Iowa Med. School, Iowa 
City).  I hope the others who also work in this area forgive me for 
not listing their names also!

Eve Ida Barak