Post-Transcriptional and Post-Translational Control

Gene expression continues to be regulated after RNA is transcribed and after protein is synthesized. Post-transcriptional control shapes the processing, transport, and fate of RNA, while post-translational control modifies, localizes, and degrades the finished protein — together fine-tuning the identity and amount of functional gene products beyond what transcription alone determines.

Definition

Post-transcriptional and post-translational control comprise the regulatory processes acting on RNA after transcription (processing, modification, stability, and translation) and on proteins after synthesis (covalent modification, localization, and degradation) to determine the final complement of active gene products.

Scope

This topic covers post-transcriptional events such as alternative splicing, RNA editing, the action of RNA-binding proteins and small regulatory RNAs, and post-translational events including covalent protein modification (notably phosphorylation) and regulated protein degradation through the ubiquitin-proteasome system. It is a mechanistic molecular topic and not clinical guidance.

Core questions

• How does one gene give rise to several different protein products?
• How is the activity of a protein switched on or off after it has been made?
• How does the cell rapidly remove proteins that are no longer needed?
• How do RNA-binding proteins and small RNAs shape the fate of transcripts?

Key concepts

• Alternative splicing
• RNA editing and chemical modification of RNA
• RNA-binding proteins
• Regulation by microRNAs
• Protein phosphorylation and other covalent modifications
• Ubiquitin-proteasome degradation
• Regulated protein localization

Mechanisms

After transcription, a primary transcript is processed and can be spliced in alternative ways to yield distinct messenger RNAs, expanding the protein repertoire from a single gene; RNA editing and modification further diversify transcripts. RNA-binding proteins, recognizing sequence and structural features through modular domains, govern splicing, transport, localization, stability, and translation, and small RNAs such as microRNAs repress targeted transcripts. Once a protein is synthesized, its function is regulated post-translationally: reversible covalent modifications, of which phosphorylation by the large family of protein kinases is the most widespread, change activity, interactions, or localization. Protein abundance is also controlled by regulated destruction — tagging proteins with ubiquitin marks them for degradation by the proteasome, providing a rapid and selective means to terminate a protein's action. Together these mechanisms determine which gene products are present, in what form, and for how long.

Clinical relevance

Defects in splicing, in protein modification, and in the ubiquitin-proteasome system are implicated in numerous diseases, and these mechanisms are central to how cells control signaling and protein quality. This entry is educational background and is not a basis for individual diagnostic or treatment decisions.

History

Through the late twentieth century, gene expression was shown to be controlled well beyond transcription: alternative splicing was found to diversify proteins from single genes, the ubiquitin-proteasome system (work recognized with the 2004 Nobel Prize in Chemistry) was characterized by Hershko and Ciechanover, and protein phosphorylation emerged as a dominant regulatory modification. Genome-scale surveys such as Manning and colleagues' catalogue of the human kinome (2002), reviews of RNA-binding proteins, and the discovery of microRNA regulation extended the post-transcriptional and post-translational picture.

Key figures

• Aaron Ciechanover
• Avram Hershko
• Tony Hunter
• David Bartel

Seminal works

• hershko-ciechanover-1998
• manning-2002
• bartel-2009

Frequently asked questions

How can one gene produce more than one protein?

Alternative splicing can join the gene's exons in different combinations, and RNA editing and modification add further variation, so a single gene can yield several distinct messenger RNAs and protein products.

How is a protein's activity controlled after it is made?

Through post-translational mechanisms such as reversible covalent modification (for example phosphorylation), changes in localization, and regulated degradation by the ubiquitin-proteasome system.