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Trans-regulatory element

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Trans-regulatory elements are genes which may modify (or regulate) the expression of distant genes.[1] More specifically, trans-regulatory elements are DNA sequences that encode trans-acting factors (often proteins such as transcription factors).

Trans-regulatory elements work through an intermolecular interaction between two different molecules and so are said to be "acting in trans". For example (1) a transcribed and translated transcription factor protein derived from the trans-regulatory element; and a (2) DNA regulatory element that is adjacent to the regulated gene. This is in contrast to cis-regulatory elements that work through an intramolecular interaction between different parts of the same molecule: (1) a gene; and (2) an adjacent regulatory element for that gene in the same DNA molecule.

Examples of trans-acting factors include the genes for:[2]

  • Subunits of RNA polymerase
  • Proteins that bind to RNA polymerase to stabilize the initiation complex
  • Proteins that bind to all promoter of specific sequences, but not to RNA polymerase (TFIID factors)
  • Proteins that bind to a few promoters and are required for transcription initiation (positive regulators of gene expression)

Examples

Trans-acting factors in alternative splicing in mRNA. Alternative splicing is a key mechanism that is involved in gene expression regulation. In the alternative splicing, trans-acting factors such as SR protein, hnRNP and snRNP control this mechanism by acting in trans. SR protein promotes the spliceosome assembly by interacting with snRNP(e.g. U1, U2) and splicing factors(e.g. U2AF65), and it can also antagonize the activity of hnRNP that inhibits splicing.

Trans-acting factors can be categorized by their interactions with the regulated genes, cis-acting elements of the genes, or the gene products.

DNA binding

DNA binding trans-acting factors regulate gene expression by interfering with the gene itself or cis-acting elements of the gene, which lead to changes in transcription activities. This can be direct initiation of transcription.[3] promotion or repression of transcriptional protein activities.[4]

Specific examples include:

DNA editing

DNA editing proteins edit and permanently change gene sequence, and subsequently the gene expression of the cell.[5][6] All progenies of the cell will inherit the edited gene sequence.[7] DNA editing proteins often take part in the immune response system of both prokaryotes and eukaryotes, providing high variance in gene expression in adaptation to various pathogens.[8]

Specific examples include:

mRNA processing

Main article: Messenger RNA

mRNA processing acts as a form of post-transcriptional regulation, which mostly happens in eukaryotes. 3′ cleavage/polyadenylation and 5’ capping increase overall RNA stability, and the presence of 5’ cap allows ribosome binding for translation. RNA splicing allows the expression of various protein variants from the same gene.[9]

Specific examples include:

mRNA binding

mRNA binding allows repression of protein translation through direct blocking, degradation or cleavage of mRNA.[10][11] Certain mRNA binding mechanisms have high specificity, which can act as a form of the intrinsic immune response during certain viral infections.[12] Certain segmented RNA viruses can also regulate viral gene expression through RNA binding of another genome segment, however, the details of this mechanism are still unclear.[13]

Specific examples include:

See also

References

  1. ^ Gilad Y, Rifkin SA, Pritchard JK (August 2008). "Revealing the architecture of gene regulation: the promise of eQTL studies". Trends Genet. 24 (8): 408–15. doi:10.1016/j.tig.2008.06.001. PMC 2583071. PMID 18597885.
  2. ^ McClean, Phillip. "Cis-Acting element and trans-acting factors". 1998.
  3. ^ Griffiths AJ, Miller JH, Suzuki DT, Lewontin RC, Gelbart WM (2000). "Transcription and RNA polymerase". An Introduction to Genetic Analysis (7th ed.). New York: W. H. Freeman. ISBN 978-0-7167-3520-5.
  4. ^ Lodish H, Berk A, Zipursky SL, Berk A, Darnell JE, Zipursky SL, Baltimore D, Matsudaira P (2000). "Section 10.5: Eukaryotic Transcription Activators and Repressors". Molecular Cell Biology (4th ed.). New York: W. H. Freeman. ISBN 978-0-7167-3136-8.
  5. ^ Roth DB (December 2014). "V(D)J Recombination: Mechanism, Errors, and Fidelity". Microbiology Spectrum. 2 (6). doi:10.1128/microbiolspec.MDNA3-0041-2014. PMC 5089068. PMID 26104458.
  6. ^ McGinn J, Marraffini LA (January 2019). "Molecular mechanisms of CRISPR-Cas spacer acquisition". Nature Reviews. Microbiology. 17 (1): 7–12. doi:10.1038/s41579-018-0071-7. PMID 30171202.
  7. ^ Janeway Jr CA, Travers P, Walport M, Schlomchik M (2001). "B-cell activation by armed helper T cells". Immunobiology: The Immune System in Health and Disease (5th ed.). New York: Garland Science. ISBN 978-0-8153-3642-6.
  8. ^ Janeway Jr CA, Travers P, Walport M, Schlomchik M (2001). "The generation of diversity in immunoglobulins". Immunobiology: The Immune System in Health and Disease (5th ed.). New York: Garland Science. ISBN 978-0-8153-3642-6.
  9. ^ Lodish H, Berk A, Zipursky SL, Berk A, Darnell JE, Zipursky SL, Baltimore D, Matsudaira P (2000). "Section 11.2: Processing of Eukaryotic mRNA". Molecular Cell Biology (4th ed.). New York: W. H. Freeman. ISBN 978-0-7167-3136-8.
  10. ^ Dana H, Chalbatani GM, Mahmoodzadeh H, Karimloo R, Rezaiean O, Moradzadeh A, Mehmandoost N, Moazzen F, Mazraeh A, Marmari V, Ebrahimi M, Rashno MM, Abadi SJ, Gharagouzlo E (June 2017). "Molecular Mechanisms and Biological Functions of siRNA". International Journal of Biomedical Science : IJBS. 13 (2): 48–57. PMC 5542916. PMID 28824341.
  11. ^ Wahid F, Shehzad A, Khan T, Kim YY (November 2010). "MicroRNAs: synthesis, mechanism, function, and recent clinical trials". Biochimica Et Biophysica Acta. 1803 (11): 1231–43. doi:10.1016/j.bbamcr.2010.06.013. PMID 20619301.
  12. ^ Guo XK, Zhang Q, Gao L, Li N, Chen XX, Feng WH (January 2013). "Increasing expression of microRNA 181 inhibits porcine reproductive and respiratory syndrome virus replication and has implications for controlling virus infection". Journal of Virology. 87 (2): 1159–71. doi:10.1128/JVI.02386-12. PMC 3554091. PMID 23152505.
  13. ^ Newburn LR, White KA (August 2019). "Trans-Acting RNA-RNA Interactions in Segmented RNA Viruses". Viruses. 11 (8). doi:10.3390/v11080751. PMC 6723669. PMID 31416187.{{cite journal}}: CS1 maint: unflagged free DOI (link)


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