Page 106 - Academic Press Encyclopedia of Physical Science and Technology 3rd Molecular Biology

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Encyclopedia of Physical Science and Technology EN017F-788 August 3, 2001 16:27

Translation of RNA to Protein 47

be favored, which may act either to stabilize or destabilize During the cell cycle, histone mRNA is destabilized
the mRNA, according to the needs of the cell, by determin- after completion of DNA replication, resulting in a 30-
ing its susceptibility to degradative enzymes (often termed to 50-fold decrease. This change appears to be due to an
trans-acting factors). increase in the level of free histones, which form a com-
Whereas the structure of mRNA determines its suscep- plex with histone mRNA by interaction with a stem–loop

tibility to degradative enzymes, the detailed mechanisms structure at the extreme 3 terminus. Formation of this
arecomplex.Inprokaryotes,theenzymesinvolvedinclude histone–histone mRNA complex is thought to activate a
two endonucleases (RNase E and RNase III) and two ex- ribsome-associated 3 → 5 -exonuclease, which degrades

onucleases (polynucleotide phosphorylase and RNase II). the histone mRNA. During the S phase, newly synthesized
Other nucleases may be active in particular cases such as DNA binds free histones to form nucleosomes, thus pre-
phage infection. In eukaryotes, a major pathway involves venting the degradation of histone mRNA at this stage of

removal of the 3 poly(A) tail (deadenylation), followed the cell cycle.

by removal of the 5 cap, which renders the mRNA suscep- Specific regulation of gene expression at the level of
tible to rapid endonucleolytic degradation in the 5 → 3 translation also exists in prokaryotes. For example, the

direction. synthesisofE.colithreonyl-tRNAsynthetaseisnegatively
autoregulated by an interaction of the tRNA-like leader
sequence of its mRNA with the synthetase, which in-
B. Control by Interaction of Proteins
hibits translation by preventing the binding of ribosomes.
with mRNA Thr
The synthetase is displaced from the mRNA by tRNA ,
Throughout the ribosome cycle, dynamic protein–mRNA which thus acts as a translational antirepressor. This reg-
interactions are functionally important in the initiation, ulatory mechanism allows the cell to maintain a balance
elongation, and termination of polypeptide synthesis. between the tRNA synthetase and its cognate tRNA.
In addition, more stable associations between proteins Similarly, there is a mechanism used to control the
and mRNAs have been observed, particularly in eukary- synthesis of proteins encoded by a polycistronic mRNA.
otic cells. These messenger ribonucleoprotein complexes In this case, selective binding of the ribosomal protein
(mRNPs) occur both in polyribosomes and free in the to the region of the mRNA involved in the initiation of
cytosol, some of the latter being either temporarily or translation leads to the regulatory protein controlling both
permanently unavailable for translation. Thus, protein- its own synthesis and that of other ribosomal proteins.
mRNA interactions contribute to the efficiency with which A specific example is the role of ribosomal protein S4,
mRNAs are translated. which acts as a translational repressor of four riboso-
Some proteins, such as the poly(A)-binding protein mal proteins (S4, S11, S13, and L17). Protein S4 appears
(p78), are present in most if not all mRNPs, whereas others to function as a repressor through an unusual “pseudo-
appear to be cell specific and mRNA selective. In unfer- knot” linking a hairpin loop upstream of the ribosome-
tilized sea urchin eggs and Xenopus oocytes, for example, binding site with sequences 2 to 10 codons downstream
untranslated messenger is sequestered by association with of the initiation codon. (A pseudoknot structure contains
proteins that prevent translation until later stages of devel- intramolecular base pairs between base residues in the
opment. Duck reticulocytes contain globin mRNP, which loop of a stem–loop structure and distal complementary
cannot be translated in vitro, whereas the mRNA obtained regions of the RNA.) Stabilization of this structure by S4
by deproteinizing the complex can be translated, show- would prevent the binding of ribosomes, and this control
ing that in this case translation is prevented by the mRNP mechanism may contribute to the coordinated synthesis
proteins. of the different ribosomal proteins required for ribosome
Formation of a site-specific mRNA-protein complex is assembly.
involved in the translational control of the biosynthesis
of ferritin, an iron storage protein, which is stimulated in C. Control by mRNA Structure
response to the presence of iron. In this instance, a cy-
toplasmic repressor protein of 85 kDa binds to a highly The secondary structure of some eukaryotic mRNAs reg-
conserved 28-nucleotide stem–loop structure in the 5 un- ulates translation by a mechanism involving a riboso-

translated region of ferritin mRNAs in the absence of iron. mal frameshift which gives rise to a directed change
In the presence of iron, the protein dissociates from the of the translational reading frame to allow the synthe-
mRNA, which is then available for translation. A similar sis of a single protein from two or more overlapping
loop motif occurs in the 3 untranslated region of transfer- genes by suppression of an intervening termination codon.

rin receptor mRNA, which is also subject to translational Several retroviruses use this mechanism to move from one
control by an iron-responsive repressor. reading frame to another in the expression of the viral