Post‐Transcriptional Regulation of Gene Expression and Human Genetic Disease


Despite the fact that all cells in an organism contain the same genetic information, the cells that comprise any organism have vastly distinct form and function. This diversity of form function is achieved because only a subset of the genetic information is transcribed into messenger RNA (mRNA) and translated into protein at any given time in any cell. While this regulation of gene expression occurs at many levels, extensive regulation occurs after an mRNA is produced prior to translation of that mRNA into protein. These regulatory events include nuclear processing to produce a mature mRNA, export to the cytoplasm, and a variety of potential fates in the cytoplasm including translation to protein and, ultimately, decay. All these regulatory events are termed post‐transcriptional regulation. Increasingly mutations in genes that encode components of this carefully orchestrated post‐transcriptional regulatory pathway are being linked to human disease, highlighting the importance of post‐transcriptional processing events.

Key Concepts

  • While all cells in an organism contain the same genetic material, these cells have vastly distinct forms and functions.
  • There is extensive post‐transcriptional processing to produce a mature mRNA that occurs post‐transcriptionally.
  • Numerous regulatory events in both the nucleus and the cytoplasm dictate when, where, and if an mRNA is translated into protein.
  • Most mature mRNAs are produced through extensive processing steps that occur in the nucleus prior to export to the cytoplasm.
  • There are many potential fates for an mRNA in the cytoplasm including transport to a specific cellular location, storage in cytoplasmic bodies/granules, translation and destruction.
  • Turnover/decay of mRNA is a key regulatory step that contributes to the regulation of gene expression.
  • Numerous mutations have been identified in genes encoding key post‐transcriptional processing factors linking post‐transcriptional processing to a variety of human diseases.
  • Mutations in genes that encode key post‐transcriptional regulatory factors often cause tissue‐specific pathology.
  • Many years of effort to define key pathways in post‐transcriptional regulation are starting to come to fruition in the realm of targeting these pathways for drug development.
  • Gene expression and post‐transcriptional processing events are now the targets of successful therapies to treat some devastating diseases with many more exciting advances on the horizon.

Keywords: gene expression; post‐transcriptional regulation; RNA processing; human genetic disease; mRNA export; translational control; RNA decay

Figure 1. Schematic representation of mRNA post‐transcriptional processing and gene expression. (A) As the 5′ end of an mRNA transcript emerges from RNA polymerase II, capping enzymes add a 7‐methylguanosine 5′ cap via a 5′ to 5′ triphosphate linkage. (B) As transcription continues, the mRNA is cotranscriptionally spliced to remove introns. (C) At the 3′ end of the transcript, cleavage and polyadenylation are coupled to release the mRNA from the site of transcription and add an untemplated poly(A) tail. (D) Once nuclear processing events are complete and the mature mRNA is packaged with appropriate export factors, the mRNP complex is exported to the cytoplasm through nuclear pore complexes embedded in the nuclear envelope. Once in the cytoplasm, there are a number of fates for the mRNA, including (E) translation; (F) localization to a specific location; or (G) storage in cytoplasmic bodies such as P bodies. These processes have extensive interplay, meaning that an mRNA can be localised and then translated or move into and out of storage depots. Ultimately, (H) mRNA is degraded in the cytoplasm.


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Sterrett, Maria C, and Corbett, Anita H(Nov 2019) Post‐Transcriptional Regulation of Gene Expression and Human Genetic Disease. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0028665]