post-translational modification

Examples of post-translational modification in the following topics:

• Cancer and Translational Control

  • There are many examples of translational or post-translational modifications of proteins that arise in cancer.
  • Modifications are found in cancer cells from the increased translation of a protein to changes in protein phosphorylation to alternative splice variants of a protein.

• Regulating Protein Activity and Longevity

  • Chemical modifications occur in response to external stimuli such as stress, the lack of nutrients, heat, or ultraviolet light exposure.
  • These changes can alter protein function, epigenetic accessibility, transcription, mRNA stability, or translation; all resulting in changes in expression of various genes.
  • Because proteins are involved in every stage of gene regulation, the phosphorylation of a protein (depending on the protein that is modified) can alter accessibility to the chromosome, can alter translation (by altering transcription factor binding or function), can change nuclear shuttling (by influencing modifications to the nuclear pore complex), can alter RNA stability (by binding or not binding to the RNA to regulate its stability), can modify translation (increase or decrease), or can change post-translational modifications (add or remove phosphates or other chemical modifications).
  • Another example of chemical modifications affecting protein activity include the addition or removal of methyl groups.
  • Methyl groups are added to proteins via the process of methylation; this is the most common form of post-translational modification.

• Prokaryotic versus Eukaryotic Gene Expression

  • To synthesize a protein, the processes of transcription (DNA to RNA) and translation (RNA to protein) occur almost simultaneously.
  • The newly-synthesized RNA is then transported out of the nucleus into the cytoplasm where ribosomes translate the RNA into protein.
  • The processes of transcription and translation are physically separated by the nuclear membrane; transcription occurs only within the nucleus, and translation occurs only outside the nucleus within the cytoplasm.
  • Regulation may occur when the DNA is uncoiled and loosened from nucleosomes to bind transcription factors (epigenetics), when the RNA is transcribed (transcriptional level), when the RNA is processed and exported to the cytoplasm after it is transcribed (post-transcriptional level), when the RNA is translated into protein (translational level), or after the protein has been made (post-translational level).
  • Further regulation may occur through post-translational modifications of proteins.

• Cell Signaling and Gene Expression

  • To synthesize a protein, the processes of transcription and translation occur almost simultaneously.
  • The processes of transcription and translation are physically separated by the nuclear membrane: transcription occurs only within the nucleus, and translation occurs only outside the nucleus in the cytoplasm.
  • Regulation may occur when the DNA is uncoiled and loosened from nucleosomes to bind transcription factors (epigenetic level); when the RNA is transcribed (transcriptional level); when the RNA is processed and exported to the cytoplasm after it is transcribed (post-transcriptional level); when the RNA is translated into protein (translational level); or after the protein has been made (post-translational level).
  • Prokaryotic transcription and translation occur simultaneously in the cytoplasm; regulation occurs at the transcriptional level.
  • Further regulation may occur through post-translational modifications of proteins.

• Cancer and Post-Transcriptional Control

  • Modifications, such as the overexpression of miRNAs, in the post-transcriptional control of a gene can result in cancer.
  • Post-transcriptional regulation is the control of gene expression at the RNA level; therefore, between the transcription and the translation of the gene.
  • After being produced, the stability and distribution of the different transcripts is regulated (post-transcriptional regulation) by means of RNA-binding proteins (RBP) that control the various steps and rates of the transcripts: events such as alternative splicing, nuclear degradation (exosome), processing, nuclear export (three alternative pathways), sequestration in DCP2-bodies for storage or degradation, and, ultimately, translation.
  • Changes in the post-transcriptional control of a gene can result in cancer.

• Altered Gene Expression in Cancer

  • This can be the result of gene mutation or changes in gene regulation (epigenetic, transcription, post-transcription, translation, or post-translation).
  • Changes in epigenetic regulation, transcription, RNA stability, protein translation, and post-translational control can be detected in cancer.
  • Therefore, changes in histone acetylation (epigenetic modification that leads to gene silencing), activation of transcription factors by phosphorylation, increased RNA stability, increased translational control, and protein modification can all be detected at some point in various cancer cells.
  • Scientists are working to understand the common changes that give rise to certain types of cancer or how a modification might be exploited to destroy a tumor cell.
  • Overexpression of the oncogene can lead to uncontrolled cell growth because oncogenes can alter transcriptional activity, stability, or protein translation of another gene that directly or indirectly controls cell growth.

• Protein Folding, Modification, and Targeting

  • After being translated from mRNA, all proteins start out on a ribosome as a linear sequence of amino acids.
  • During and after translation, individual amino acids may be chemically modified and signal sequences may be appended to the protein.
  • Discuss how post-translational events affect the proper function of a protein

• The Process and Purpose of Gene Expression Regulation

  • Gene expression is a highly complex, regulated process that begins with DNA transcribed into RNA, which is then translated into protein.
  • For the proteins to be expressed, the DNA must be transcribed into RNA and the RNA must be translated into protein.
  • In a given cell type, not all genes encoded in the DNA are transcribed into RNA or translated into protein because specific cells in our body have specific functions.
  • At any given time, only a subset of all of the genes encoded by our DNA are expressed and translated into proteins.
  • In this section, you will learn about the various methods of gene regulation and the mechanisms used to control gene expression, such as: epigenetic, transcriptional, post-transcriptional, translational, and post-translational controls in eukaryotic gene expression, and transcriptional control in prokaryotic gene expression.

• Processing of tRNAs and rRNAs

  • rRNA and tRNA are structural molecules that aid in protein synthesis but are not themselves translated into protein.
  • The tRNAs and rRNAs are structural molecules that have roles in protein synthesis; however, these RNAs are not themselves translated.
  • In all organisms, tRNAs are transcribed in a pre-tRNA form that requires multiple processing steps before the mature tRNA is ready for use in translation.
  • The most common modifications are the conversion of adenine (A) to pseudouridine (ψ), the conversion of adenine to inosine (I), and the conversion of uridine to dihydrouridine (D).
  • But over 100 other modifications can occur.

• RNA Splicing

  • Genetic Information flows from DNA to RNA by the process of transcription and then from RNA to protein by the process of translation.
  • In order to ensure that the proper products are produced, gene expression is regulated at many different stages during and in between transcription and translation.
  • Thus, splicing is the first stage of post-transcriptional control.
  • For example, if a pre-mRNA has four exons (A, B, C, and D), these can be spliced and translated in a number of different combinations.
  • Exons A, B, and C can be translated together or Exons A, C, and D can be translated.