TOPs and their regulation.
Upon cell-cycle arrest or nutrient deprivation, the cellular rate of ribosome production is reduced significantly. In mammalian cells, this effect is achieved in part through a co-ordinated inhibition of RP (ribosomal protein) synthesis. More specifically, translation initiation on RP mRNAs is inhibited. Translational regulation of RP synthesis is dependent on cis-elements within the 5'-UTRs (5'-untranslated regions) of the RP mRNAs. In particular, a highly conserved 5'-TOP (5'-terminal oligopyrimidine tract) appears to play a key role in the regulation of RP mRNA translation. This article explores recent developments in our understanding of the mechanism of TOP mRNA regulation, focusing on upstream signalling pathways and trans-acting factors, and highlighting some interesting observations which have come to light following the recent development of cDNA microarray technology coupled with polysome analysis.
Hamilton
T L
TL
School of Pharmacy, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
Stoneley
M
M
Spriggs
K A
KA
Bushell
M
M
D020121:5' Untranslated Regions; D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D015394:Molecular Structure; D011132:Polyribosomes / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D011743:Pyrimidines / Q000378:metabolism*; D012315:RNA Caps / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D020121:5' Untranslated Regions; D011743:Pyrimidines; D012315:RNA Caps; D012333:RNA, Messenger; D012269:Ribosomal Proteins