Relationships and implications for the origin of the genetic code. Gene : 63 — Sequence, structure, and context preferences of human RNA binding proteins. Mol Cell 70 : — Identifying nonpolar transbilayer helices in amino acid sequences of membrane proteins. Annu Rev Biophys Biophys Chem 15 : — Position-dependent splicing activation and repression by SR and hnRNP proteins rely on common mechanisms.
RNA 19 : 96 — Context-dependent control of alternative splicing by RNA-binding proteins. Nat Rev Genet 15 : — The hnRNP family: insights into their role in health and disease. Hum Genet : — Database Oxford : baw Comparative analysis identifies exonic splicing regulatory sequences—the complex definition of enhancers and silencers. Mol Cell 22 : — Nucleic Acids Res 39 : — Nat Commun 6 : Nucleic Acids Res 43 : D — D A highly conserved program of neuronal microexons is misregulated in autistic brains.
Cell : — Itzkovitz S , Alon U. The genetic code is nearly optimal for allowing additional information within protein-coding sequences. Genome Res 17 : — Overlapping codes within protein-coding sequences.
Genome Res 20 : — The mechanisms of a mammalian splicing enhancer. Nucleic Acids Res 46 : — Analysis and design of RNA sequencing experiments for identifying isoform regulation. Nat Methods 7 : — J Mol Biol : — Kyte J , Doolittle RF. A simple method for displaying the hydropathic character of a protein. Locating protein-coding sequences under selection for additional, overlapping functions in 29 mammalian genomes. Genome Res 21 : — Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB.
Nat Struct Mol Biol 17 : — SRSF2 regulates alternative splicing to drive hepatocellular carcinoma development. Cancer Res 77 : — Endothelial, epithelial, and fibroblast cells exhibit specific splicing programs independently of their tissue of origin. Genome Res 24 : — Molecular basis for specificity of nuclear import and prediction of nuclear localization. Biochim Biophys Acta : — Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing.
Nat Genet 40 : — Genome-wide analysis reveals SR protein cooperation and competition in regulated splicing. Mol Cell 50 : — Splicing and the evolution of proteins in mammals. PLoS Biol 5 : e J Mol Recognit 17 : 17 — Prilusky J , Bibi E. Studying membrane proteins through the eyes of the genetic code revealed a strong uracil bias in their coding mRNAs.
Proc Natl Acad Sci : — R Core Team. R: a language and environment for statistical computing. R Foundation for Statistical Computing , Vienna. Google Scholar. A compendium of RNA-binding motifs for decoding gene regulation. Nature : — RNA Biol 11 : — Savisaar R , Hurst LD.
Both maintenance and avoidance of RNA-binding protein interactions constrain coding sequence evolution. Mol Biol Evol 34 : — Estimating the prevalence of functional exonic splice regulatory information.
Exonic splice regulation imposes strong selection at synonymous sites. Genome Res 28 : — Sounds of silence: synonymous nucleotides as a key to biological regulation and complexity. Nucleic Acids Res 41 : — Splice junctions are constrained by protein disorder. Nucleic Acids Res 43 : — Taylor FJ , Coates D.
The code within the codons. Biosystems 22 : — Thapar R. Structural basis for regulation of RNA-binding proteins by phosphorylation. ACS Chem Biol 10 : — Identification of protein features encoded by alternative exons using Exon Ontology. Genome Res 27 : — Protein Pept Lett 13 : — Alternative isoform regulation in human tissue transcriptomes. Finding exonic islands in a sea of non-coding sequence: splicing related constraints on protein composition and evolution are common in intron-rich genomes.
Genome Biol 9 : R Woese CR. Order in the genetic code. Proc Natl Acad Sci 54 : 71 — Water, protein folding, and the genetic code. Science : — Zhang Z , Yu J. On the organizational dynamics of the genetic code.
Genomics Proteomics Bioinformatics 9 : 21 — Prediction of clustered RNA-binding protein motif sites in the mammalian genome.
However, it is becoming clear that at least some of it is integral to the function of cells, particularly the control of gene activity. For example, noncoding DNA contains sequences that act as regulatory elements, determining when and where genes are turned on and off.
Such elements provide sites for specialized proteins called transcription factors to attach bind and either activate or repress the process by which the information from genes is turned into proteins transcription. Noncoding DNA contains many types of regulatory elements:.
Promoters provide binding sites for the protein machinery that carries out transcription. Promoters are typically found just ahead of the gene on the DNA strand. Enhancers provide binding sites for proteins that help activate transcription. Enhancers can be found on the DNA strand before or after the gene they control, sometimes far away. Silencers provide binding sites for proteins that repress transcription. Like enhancers, silencers can be found before or after the gene they control and can be some distance away on the DNA strand.
Insulators provide binding sites for proteins that control transcription in a number of ways. Some prevent enhancers from aiding in transcription enhancer-blocker insulators. Others prevent structural changes in the DNA that repress gene activity barrier insulators. Some insulators can function as both an enhancer blocker and a barrier. Some structural elements of chromosomes are also part of noncoding DNA. Molecules can interfere with RNA polymerase binding. An inactive repressor protein blue can become activated by another molecule red circle.
This active repressor can bind to a region near the promoter called an operator yellow and thus interfere with RNA polymerase binding to the promoter, effectively preventing transcription.
For an example of how this works, imagine a bacterium with a surplus of amino acids that signal the turning "on" of some genes and the turning "off" of others. In this particular example, cells might want to turn "on" genes for proteins that metabolize amino acids and turn "off" genes for proteins that synthesize amino acids.
Some of these amino acids would bind to positive regulatory proteins called activators. This binding facilitates RNA polymerase activity and transcription of nearby genes. At the same time, however, other amino acids would bind to negative regulatory proteins called repressors , which in turn bind to regulatory sites in the DNA that effectively block RNA polymerase binding Figure 3.
The control of gene expression in eukaryotes is more complex than that in prokaryotes. In general, a greater number of regulatory proteins are involved, and regulatory binding sites may be located quite far from transcription promoter sites. Also, eukaryotic gene expression is usually regulated by a combination of several regulatory proteins acting together, which allows for greater flexibility in the control of gene expression.
Figure 4: The complexity of multiple regulators Transcriptional regulators can each have a different role. Combinations of one, two, or three regulators blue, green, and yellow shapes can affect transcription in different ways by differentially affecting a mediator complex orange , which is also composed of proteins. The effect is that the same gene can be transcribed in multiple ways, depending on the combination, presence, or absence of various transcriptional regulator proteins.
As previously mentioned, enhancer sequences are DNA sequences that are bound by an activator protein, and they can be located thousands of base pairs away from a promoter, either upstream or downstream from a gene. Activator protein binding is thought to cause DNA to loop out, bringing the activator protein into physical proximity with RNA polymerase and the other proteins in the complex that promote the initiation of transcription Figure 4. Different cell types express characteristic sets of transcriptional regulators.
In fact, as multicellular organisms develop, different sets of cells within these organisms turn specific combinations of regulators on and off. Such developmental patterns are responsible for the variety of cell types present in the mature organism Figure 5.
Figure 5: Transcriptional regulators can determine cell types The wide variety of cell types in a single organism can depend on different transcription factor activity in each cell type.
Different transcription factors can turn on at different times during successive generations of cells. As cells mature and go through different stages arrows , transcription factors colored balls can act on gene expression and change the cell in different ways. This change affects the next generation of cells derived from that cell. In subsequent generations, it is the combination of different transcription factors that can ultimately determine cell type.
This page appears in the following eBook. Aa Aa Aa. Gene Expression. How Is Gene Expression Regulated? Figure 1: An overview of the flow of information from DNA to protein in a eukaryote.
Figure 2: Modulation of transcription. An activator protein bound to DNA at an upstream enhancer sequence can attract proteins to the promoter region that activate RNA polymerase green and thus transcription. Figure 4: The complexity of multiple regulators. Transcriptional regulators can each have a different role. Figure 5: Transcriptional regulators can determine cell types.
The wide variety of cell types in a single organism can depend on different transcription factor activity in each cell type. To live, cells must be able to respond to changes in their environment.
Regulation of the two main steps of protein production — transcription and translation — is critical to this adaptability. Cells can control which genes get transcribed and which transcripts get translated; further, they can biochemically process transcripts and proteins in order to affect their activity.
Regulation of transcription and translation occurs in both prokaryotes and eukaryotes, but it is far more complex in eukaryotes. Cell Biology for Seminars, Unit 2. Topic rooms within Cell Biology Close. No topic rooms are there.
0コメント