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MCAT TOPIC REVIEWS & RESOURCES

Biological and Biochemical Foundations of Living Systems

BIO
Control of Gene Expression in Eukaryotes

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Eukaryotic control of gene expression occurs by regulating the processes of transcription and translation, having opportunity to affect, first, what mRNA transcripts are produced (or not) and, second, what final protein product is derived from those transcripts.

Transcriptional regulation

Transcription in eukaryotes can be regulated more broadly by chromatin accessibility determined by how tightly (heterochromatin: less accessible) or loosely (euchromatin: more accessible) the DNA is compacted, or more expressly by the interaction of a variety of transcription factors that influence transcriptional activity of specific regions.

DNA binding proteins, transcription factors

Transcription factors are DNA binding proteins that bind to specific regions of the DNA to influence transcription:

  • activators bind in order to activate transcription
  • repressors bind in order to repress transcription

The DNA itself also assists in the regulatory process by providing binding sites for transcription factors to bind:

  • enhancers are binding sites for activators
  • silencers are binding sites for repressors

Gene amplification and duplication

Gene amplification is a structural change to DNA that gives way to duplicate copies a gene being present, which in turn can lead to an increase in transcription and protein product for that gene.

Post-transcriptional control, basic concept of splicing (introns, exons)

An mRNA transcript can itself be the target of regulation. With RNA being a single-stranded nucleic acid subject to degradation, increases to mRNA stability will improve rates of translation while destructive targeting by small regulatory RNA (microRNAs or miRNAs) will decrease translation.

Control of gene expression by mRNA processing involves modifications to the mRNA transcript. Additions of a 5'-Cap and Poly-A Tail to the ends of the mRNA have a protective effect for the transcript. Splicing determines exactly what sequences in the mRNA transcript will dictate the final mature mRNA to be translated. Introns are sequences in the mRNA that are removed (staying in the nucleus), while exons remain in the transcript (exiting the nucleus as part of the transcript to be expressed). Alternate splicing is a powerful regulation mechanism whereby different exons are selected for the mature mRNA, creating the possibility for multiple protein products arising from the same pre-mRNA transcript.

Translation itself can be targeted by regulation of the initiation factors required to bring together the mRNA and ribosomal subunits.

Additionally, protein modification by cleaving polypeptide chain or chemically tagging specific amino acids can affect activity of the gene product.

Cancer as a failure of normal cellular controls, oncogenes, tumor suppressor genes

Oncogenes and tumor suppressor genes are genes whose expression has an affect on cell division. Oncogenes arise from changes (e.g. by mutation) in proto-oncogenes, converting from a harmless sequence to encoding for a product that promotes the cell cycle with a consequence of uncontrolled cell division. Tumor suppressor genes in comparison suppress the cell cycle, a control check on cell division that is lost when changes in these genes disrupt the normal function of their products. Cancer can thus occur by gain of promotion (oncogenes) or loss of suppression (tumor suppressor genes) of cell division.

Regulation of chromatin structure

As mentioned, chromatin structure is an effective way to control gene expression by controlling access for transcription machinery and can be affected by epigenetic modifications. Histone acetylation reversibly causes the uncoiling of chromatin, increasing likelihood of transcription (reversed by deacetylation).

DNA methylation

DNA methylation more permanently works to block transcription (gene silencing).

Role of non-coding RNAs

Non-coding RNAs are RNAs which do not encode for a protein product. Instead they are themselves functional molecules generally with regulatory roles around transcription and translation. These include:

  • miRNAs (microRNAs) — transcription and post-transcription effects
  • snRNAs (small nuclear RNAs) — assist in splicing
  • rRNA (ribosomal RNA) and tRNA (transfer RNA) — contribute to translation
  • snoRNAs (small nucleolar RNAs) — modify snRNAs, rRNAs, and tRNAs

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