section ; for main tools about DNA see Bioinformatics
section)
section; for main protein tools see the bioinformatics
section)|
trans-acting factor
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cis-acting element |
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general transcription factor
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promoter (at least 1 consensus sequence) |
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specific transcription factor
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response element (sometimes into another cis-acting element) |
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coactivator-----activator
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enhancer |
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corepressor-----repressor
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silencer (a.k.a. operator in Bacteria) |
)
or activation (acetylation,
methylation,
phosphorylation,
ubiquitination,
glycosylation,
ADP-ribosylation)
can generate synergistic or antagonistic interaction affinities for chromatin-associated
proteins, which in turn dictate dynamic transitions between transcriptionally
active or transcriptionally silent chromatin states. The combinatorial
nature of histone amino-terminal modifications thus reveals a "histone
code" that considerably extends the information potential of the genetic
code.
that show allelic exclusion, most genes are thought to be expressed from
both alleles when the differentiated state of the cell supports transcription
from that locus. Monoallelic expression is used to :
.
and HDV)
can function as RdRPs
in place of sulfur. Sec is cotranslationally incorporated at a predefined
UGA codon that has been recoded from termination to Sec insertion by species-specific
mechanisms dependent on structural elements of the mRNA. As a consequence,
selenoproteins have been exlcuded from conventional heterologous recombinant
expression in bacteria. The selenium atom endows Sec with unique biochemical
properties, including a low pKa and a high reactivity with many
electrophilic agents. The introduction of selenocysteine into recombinant
non-selenoproteins produced in Escherichia coli, as part of a small
tetrapeptide motif at the C terminus, could subsequentially be used as
a protein tag for purification of the recombinant protein, selenolate-targeted
labeling with fluorescent compounds or radiolabeling with either g-emitting
75Se
or short-lived positron emitters such as 11C.
gVYb guide RNA (gRNA) directs the insertion and excision of uridines,
AID
substrate, etc.)
subunit 2 / GluR-B, HDV,
etc.) by members of the adenosine deaminases acting on RNA (ADAR)
family. Editing by ADARs is believed to occur in all metazoa, and is essential
for mammalian development. 12,723 A-to-I editing sites in 1,637 different
genes have been identified in the human transcriptome. A-to-I editing in
humans primarily occurs in noncoding regions of the RNA, typically in Alu
repeats. Analysis of the large set of editing sites indicates the role
of editing in controlling dsRNA stabilityrefU18
C/D snoRNA directs 2'-O-ribose methylation (C/D-box type) of
target rRNA, tRNA, and ncRNA by forming base pairs with sequences near
the sites to be modified (homologs have been found in archaea but not in
bacteria). In humans some are expressed exclusively in the brainsnR8
H/ACA snoRNA directs pseudouridylation of target rRNA
OxyS represses translation by forming base pair with the Shine-Dalgarno
sequence and occluding ribosome binding
DsrA sRNA activates translation by preventing formation of an inhibitory
mRNA structure
(transcriptional and posttranscriptional gene silencing (PTGS)).
MicroRNAs are abundant RNAs, varying from a few thousands to 40,000 molecules
per cellref.
They are thought to be formed from "hairpin" RNAs - RNAs that are effectively
double-stranded by virtue of the fact that they are self-complementary
and fold over in the middle. Like siRNAs, miRNAs are produced by the cleavage
of dsRNAs by Dicer and related activities. Mature microRNAs (miRNAs) are
generated via a 2-step processing pathway to yield 22-nucleotide small
RNAs that regulate gene expression at the post-transcriptional level. Initial
cleavage is catalysed by Drosha,
a nuclease of the RNase III family, which acts on primary miRNA transcripts
(pri-miRNAs) in the nucleus. Drosha exists in a multiprotein complex,
the Microprocessor, and begin the process of deconstructing that
complex into its constituent components. Along with Drosha, the Microprocessor
also contains Pasha (partner of Drosha), a dsRNA binding protein.
Suppression of Pasha expression in Drosophila cells or Caenorhabditis
elegans interferes with pri-miRNA processing, leading to an accumulation
of pri-miRNAs and a reduction in mature miRNAs. Finally, depletion or mutation
of pash-1 in C. elegans causes de-repression of a let-7
reporter and the appearance of phenotypic defects overlapping those observed
upon examination of worms with lesions in Dicer (dcr-1) or Drosha (drsh-1).
Considered together, these results indicate a role for Pasha in miRNA maturation
and miRNA-mediated gene regulationref.
miRNAs have been implicated in the control of cell death and proliferation
in flies, haematopoietic lineage differentiation in mammals, neuronal patterning
in nematodes and leaf and flower development in plants. Human Drosha is
a component of 2 multi-protein complexes. The larger complex contains multiple
classes of RNA-associated proteins including RNA helicases, proteins that
bind dsRNA, novel heterogeneous nuclear ribonucleoproteins and the Ewing's
sarcoma family of proteins. The smaller complex is composed of Drosha and
the double-stranded-RNA-binding protein, DGCR8,
the product of a gene deleted in DiGeorge syndrome. In vivo knock-down
and in vitro reconstitution studies revealed that both components
of this smaller complex, termed Microprocessor, are necessary and sufficient
in mediating the genesis of miRNAs from the primary miRNA transcriptref.
They have been found in all multicellular organisms studied, and their
encoding genes seem to make up 0.5-1% of the predicted genes in these organisms
- 200-255 in humans, for instanceref.
So far, some 175 of these human miRNAs genes have been confirmed by biochemical
analysisref.On
the basis of a model established from studies of nematode development,
miRNAs in mature animals are thought to regulate the expression of distinct
genes by base-pairing with partially complementary sequences in mRNAs and
simply inhibiting their translation into proteins. They therefore work
by a somewhat different mechanism from siRNAs, in that transcription is
not impeded and mRNAs are not destroyed. In plants, miRNAs also control
crucial developmental transitions, and in flies they control cell division
and cell deathref.
Human miRNAs were identified only a short tie ago, and little is known
about their function. As miRNAs are evolutionarily conserved, however,
there can be little doubt about their importance in human physiology. It
can be difficult to identify the precise mRNA target of miRNAs; computational
approaches to the problem are complicated by the imperfect base-pairing
between the 2. Several studies have used rules inferred from known examples
of miRNA-mRNA pairing, combined with a requirement for evolutionary conservation,
to predict possible targets. One such study predicted an average of around
5 target mRNAs per miRNAref.
Given that there are some 200 human miRNAs, it seem likley that several
thousand human mRNAs could be targeted.
expresses several miRNA genesref
RyhB sRNA,
Drosophila pseudoobscura and Anopheles gambiaeref
:
: estimates for the number of miRNAs range from hundreds to thousands
: miRNA-mediated posttranscriptional regulation of TCP4 via the JAW locus
(a 7 amino acid motif conserved at the RNA level) plays a role in normal
development.
: miR-10a and miR-196a
are encoded by genes embedded in homeobox (Hox) clusters and are expressed
in patterns that are markedly reminiscent of those of Hox genes. Furthermore,
miR-196a negatively regulates Hoxb8, indicating that its restricted
expression pattern probably reflects a role in the patterning function
of the Hox complexref.
: a brain-specific microRNA, miR-134, is localized to the synapto-dendritic
compartment of rat hippocampal neurons and negatively regulates the size
of dendritic spines—postsynaptic sites of excitatory synaptic transmission.
This effect is mediated by miR-134 inhibition of the translation of an
mRNA encoding a protein kinase, Limk1, that controls spine development.
Exposure of neurons to extracellular stimuli such as brain-derived neurotrophic
factor relieves miR-134 inhibition of Limk1 translation and in this way
may contribute to synaptic development, maturation and/or plasticityref
: researchers checked whether the same sequences that show mRNA are likely
targets of microRNAs are present in the corresponding genes of the mouse,
rat, dog and chicken. The idea that a gene is controlled by microRNAs in
humans would be supported if the same gene seemed to be controlled by microRNAs
in other animals : > 33% of human genes could be controlled by microRNAs,
which could play a role in almost every process from cell birth to cell
death, and that they might even be useful in treating human diseaseref.
This is a jump above previous estimates, such as one from last year that
put the figure at > 10% of genesref.
And because the new estimate is only a rough one, the true figure could
be much higher : the study does not identify genes regulated by microRNAs
in humans but not other animals. Indeed, microRNAs could control the action
of almost every human gene. There are currently thought to be at least
250 or so different microRNAs, but another new study suggests that there
could be 200-300 moreref
6S modulates is recognized by bacterial s70
RNA polymerase holoenzyme as an open promoter and modulated promoter use
coactivator of transcription
tmRNA consists of an alanyl-tRNA like domain, an ORF, and 4 pseudoknots
: it is initially recognized by bacterial ribosomes and EF-Tu in a manner
similar to canonical tRNAs and then acts as an mRNA (hence named tmRNA)
and alanylated tmRNA is delivered to the A site of stalled ribosomes; the
nascent polypeptide is transferred to the alanine-charged tRNA portion
of tmRNA. The problematic transcript then is replaced by the mRNA portion
of tmRNA, which encodes a tag for degradation of the stalled peptide. SmpB
acts by facilitating the contacts between tmRNA and the stalled ribosome,
and tmRNA pseudoknots play a role in the presentation of the molecule to
the ribosome, helping to orient the alanyl-tRNA like domain and the ORF.
in several different organismsref
range from 50 to 200.
-dependent
eIF6 phosphorylation, which leads to release of this protein from the 60S
subunit, allowing 80S ribosome assembly.
genes has a stem-loop secondary structure called a selenocysteine insertion
sequence (SECIS) element, which allows UGA to direct the incorporation
of selenocysteine rather than signal a translational stop.
the level of bias of genes and even the particular pattern of codon bias
can remain phylogenetically invariant for very long periods of evolution.
However, some genes, even very tightly linked genes, can change very greatly
in codon bias across species. Generally G and especially C are favored
at synonymous sites in biased genes. With the exception of aspartic acid,
all amino acids contribute significantly and about equally to the codon
usage bias of a gene. While most individual amino acids that can use G
or C at synonymous sites display a preference for C, there are exceptions:
valine and leucine, which prefer G. Smaller genes tend to be more biased
than longer genes. Mutation bias has been discounted on 3 bases: there
is little evidence of regional mutation bias in Drosophila, mutation
bias is likely toward A+T (the opposite of codon usage bias), and not all
amino acids display the preference for the same nucleotide in the wobble
position. 2 lines of evidence support a selection hypothesis based on tRNA
pools : highly biased genes tend to be highly and/or rapidly expressed,
and the preferred codons in highly biased genes optimally bind the most
abundant isoaccepting tRNAs. Genes with high codon usage bias have lower
rates of synonymous substitution between species than do genes with low
codon usage bias. Genes with higher codon usage bias display higher levels
of intraspecific synonymous polymorphism. This may be due to opposing effects
of recombinationref.-mediated
translational silencing of ceruloplasmin
(Cp) / ferroxidase expression in monocytic cells : the ribosomal
protein L13a (RPL13A) / interferon-Gamma-Activated Inhibitor of Translation
(GAIT) is phosphorylated and released from the ribosome upon IFN-g
STP, allowing it to function in ceruloplasmin
(Cp) / ferroxidase translational silencing. A multi-species analysis
has shown that, in most vertebrates, 3'-UTRs are substantially longer than
their 5' counterparts, indicating a significant potential for regulation.
In addition, the average length of 3'-UTR sequences has increased during
evolution, suggesting that their utilization might contribute to organism
complexity
(and similarly related polyketide synthesis) occurs mainly in Actinomycetes,
Bacilli
and filamentous Fungi. Nonribosomal peptides (NRP) are assembled
in the cytoplasm by large megaproteins called NRP synthetases consist
of a series of active sites called modules. Each module carries out catalysis
and modification of the tethered growing peptide chain. The small (2-48)
amino acid peptides produced include: the antibiotics penicillin, erythromycin,
and vancomycin, the immunosuppressant cyclosporin, and anticancer agents,
all of which have unusual structures.
).
Copyright © 2001-2014 Daniele Focosi.
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