Biomaterial Database

The role of the 5' untranslated region of an mRNA in translation regulation during development. 1999

A W van der Velden, and A A Thomas

Department of Molecular Cell Biology, Utrecht University, The Netherlands. a.w.vandervelden@bio.uu.nl

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 efficiency can be very specifically regulated by their 5' UTR, providing post-transcriptional regulation. During embryonic development, the 5' UTRs of Antp. Ubx RAR beta 2 c-mos and c-myc regulate protein expression in a spatio-temporal manner. Translation initiation on a number of growth factor RNAs (IGFII, PDGF2, TGF beta, 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.

UI	MeSH Term	Description	Entries
D007335	Insulin-Like Growth Factor II	A well-characterized neutral peptide believed to be secreted by the LIVER and to circulate in the BLOOD. It has growth-regulating, insulin-like and mitogenic activities. The growth factor has a major, but not absolute, dependence on SOMATOTROPIN. It is believed to be a major fetal growth factor in contrast to INSULIN-LIKE GROWTH FACTOR I, which is a major growth factor in adults.	IGF-II,Multiplication-Stimulating Activity,Somatomedin MSA,IGF-2,Insulin Like Growth Factor II,Insulin-Like Somatomedin Peptide II,Multiplication-Stimulating Factor,Somatomedin A,Factor, Multiplication-Stimulating,Insulin Like Somatomedin Peptide II,Multiplication Stimulating Activity,Multiplication Stimulating Factor
D007938	Leukemia	A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006)	Leucocythaemia,Leucocythemia,Leucocythaemias,Leucocythemias,Leukemias
D008222	Lymphokines	Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity.	Lymphocyte Mediators,Mediators, Lymphocyte
D008297	Male		Males
D009687	Nuclear Proteins	Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.	Nucleolar Protein,Nucleolar Proteins,Nuclear Protein,Protein, Nuclear,Protein, Nucleolar,Proteins, Nuclear,Proteins, Nucleolar
D010448	Peptide Initiation Factors	Protein factors uniquely required during the initiation phase of protein synthesis in GENETIC TRANSLATION.	Initiation Factors,Initiation Factor,Factors, Peptide Initiation,Initiation Factors, Peptide
D011471	Prostatic Neoplasms	Tumors or cancer of the PROSTATE.	Cancer of Prostate,Prostate Cancer,Cancer of the Prostate,Neoplasms, Prostate,Neoplasms, Prostatic,Prostate Neoplasms,Prostatic Cancer,Cancer, Prostate,Cancer, Prostatic,Cancers, Prostate,Cancers, Prostatic,Neoplasm, Prostate,Neoplasm, Prostatic,Prostate Cancers,Prostate Neoplasm,Prostatic Cancers,Prostatic Neoplasm
D002454	Cell Differentiation	Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.	Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D004268	DNA-Binding Proteins	Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.	DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man