Abstract
Cap-dependent ribosomal scanning occurs on the majority of cellular 5'UTRs. This process is severely hampered on long 5'UTRs, containing AUGs and secondary structure. These characteristics are often found in mRNAs
encoding regulatory proteins like proto-oncogenes, growth factors, their receptors, and homeodomain proteins. A number of these mRNAs use an alternative mechanism of translation initiation, involving an internal ribosomal
entry site (IRES). Cellular mRNAs containing a complex 5'UTR or an IRES share an intriguing characteristic: their translational e�ciency can be very specifically regulated by their 5'UTR, providing post-transcriptional regulation.
During embryonic development, the 5'UTRs of Antp, Ubx, RARß2, c-mos and c-myc regulate protein expression in a spatio-temporal manner. Translation initiation on a number of growth factor RNAs (IGFII, PDGF2, TGFß, FGF-2, and VEGF) is specifically regulated during differentiation, growth, and stress.
Furthermore, 5' UTR activity, mutations in the 5'UTR, or the occurrence of alternative 5'UTRs have been implicated in the progression of various forms of cancer. The mechanisms involved in 5'UTR mediated control are not well understood. Binding of trans-acting factors could mediate translation stimulation or repression. Furthermore, the precise localization of upstream AUGs and the activity of the cap-binding initiation factor 4E are suggested to be important for translation regulation of these mRNAs.
This review focuses on 5'UTRs whose activity is regulated, the processes during which this regulation occurs, and as far as known the mechanisms involved.
encoding regulatory proteins like proto-oncogenes, growth factors, their receptors, and homeodomain proteins. A number of these mRNAs use an alternative mechanism of translation initiation, involving an internal ribosomal
entry site (IRES). Cellular mRNAs containing a complex 5'UTR or an IRES share an intriguing characteristic: their translational e�ciency can be very specifically regulated by their 5'UTR, providing post-transcriptional regulation.
During embryonic development, the 5'UTRs of Antp, Ubx, RARß2, c-mos and c-myc regulate protein expression in a spatio-temporal manner. Translation initiation on a number of growth factor RNAs (IGFII, PDGF2, TGFß, FGF-2, and VEGF) is specifically regulated during differentiation, growth, and stress.
Furthermore, 5' UTR activity, mutations in the 5'UTR, or the occurrence of alternative 5'UTRs have been implicated in the progression of various forms of cancer. The mechanisms involved in 5'UTR mediated control are not well understood. Binding of trans-acting factors could mediate translation stimulation or repression. Furthermore, the precise localization of upstream AUGs and the activity of the cap-binding initiation factor 4E are suggested to be important for translation regulation of these mRNAs.
This review focuses on 5'UTRs whose activity is regulated, the processes during which this regulation occurs, and as far as known the mechanisms involved.
| Original language | English |
|---|---|
| Article number | 1357-2725/99/$ |
| Pages (from-to) | 87-106 |
| Number of pages | 20 |
| Journal | International Journal of Biochemistry & Cell Biology |
| Volume | 31 |
| Publication status | Published - 1999 |
Bibliographical note
106Keywords
- Life sciences
- Biologie/Milieukunde (BIOL)
