Researchers: Gene translation “much more complex than previously thought”

mRNA translation decodes nucleotide into amino acid sequences. However, translation has also been shown to affect mRNA stability depending on codon composition in model organisms, although universality of this mechanism remains unclear. Translation affects mRNA stability in a codon-dependent manner in human cells Qiushuang Wu, Santiago Gerardo Medina, [...], and Ariel Alejandro Bazzini translation strongly affects mRNA stability in a codon-dependent manner in human cells. Proteins are made by joining together building blocks called amino acids into strings. The proteins are ‘translated’ from genetic sequences called mRNA molecules. These sequences can be thought of as series of ‘letters’, which are read in groups of three known as codons. Molecules called tRNAs recognize the codons and add the matching amino acids to the end of the protein. Each tRNA can recognize one or several codons, and the levels of different tRNAs inside the cell vary. There are 61 codons that code for amino acids, but only 20 amino acids. This means that some codons produce the same amino acid. Despite this, there is evidence to suggest that not all of the codons that produce the same amino acid are exactly equivalent. In bacteria, yeast and zebrafish, some codons seem to make the mRNA molecule more stable, and others make it less stable. This might help the cell to control how many proteins it makes. It was not clear whether the same is true for humans. The main function of the ribosome is to translate the mRNA nucleotide sequences into the amino acid sequence. However, translation is also important for mRNA quality control, targeting defective mRNAs for degradation (Shoemaker and Green, 2012). Translation has also been shown to strongly affect mRNA stability of non-defective transcripts depending on the codon composition in model organisms These observations highlight the wealth of regulatory information residing within the coding sequence, the largest fraction of the human transcriptome. Further, this study provides insight on the regulatory role of core components, such as tRNAs and ribosomes (Figure 6). These have long been under appreciated in regulation despite their relatively high levels of expression, their abundant interactions with mRNAs, and evolutionary conservation. Future studies of this relatively unexplored mechanism of post-transcriptional regulation may be relevant to human diseases. OLV

Regulation of mRNA Translation in Neurons–A Matter of Life and Death Mridu Kapur, Caitlin E. Monaghan, and Susan L. Ackerman Neuron. 2017 Nov 1; 96(3): 616–637. doi: 10.1016/j.neuron.2017.09.057 Dynamic regulation of mRNA translation initiation and elongation is essential for the survival and function of neural cells. dysregulation of mRNA translation is emerging as a unifying mechanism underlying the pathogenesis of many neurodegenerative disorders. The proper decoding of mRNAs into proteins is critical for cellular function. This process must be carefully regulated in all cell types, but neurons are particularly reliant on the spatial and temporal control of mRNA translation due to their striking polarized morphology and the demands of synaptic plasticity. OLV

Transcription isn’t simple either: There has been much speculation concerning the kinetic pathway along which RNA polymerase locates promoter sequences embedded in nonspecific DNA. Substantial progress has been made in understanding the interaction of RNA polymerase with promoters in prokaryotes. The various intermediates which have been identified kinetically or structurally, as well as some agents or conditions which can affect their interconversion, are shown in Fig. ?Fig.11 (details concerning the effectors can be found in the legend). Several aspects of the scheme in Fig. ?Fig.11 remain unclear, however, and require further experimentation for their elucidation. The nature of the conformational change that occurs during the transition from I1 to I2 is a subject of great importance. The hypothesis that this step involves the closing of the jaw on RNA polymerase needs to be tested. How RNA polymerase weakens the base pairing interactions of DNA in order to be able to orchestrate the separation of the strands also remains to be established, as does the precise site of initiation of strand separation and the involvement of specific amino acid residues of RNA polymerase in this process. It is necessary to pinpoint the precise amino acid residue-nucleotide interactions which occur in the various intermediate initiation complexes to develop a clearer picture of the early steps of transcription. Also, it needs to be determined what triggers the release of ? factor from the initiating RNA polymerase. Finally, the role of NTPs in open-complex stabilization, start site selection, and the transition from initiation to elongation needs to be further explored. RNA Polymerase-Promoter Interactions: the Comings and Goings of RNA Polymerase Pieter L. deHaseth, Margaret L. Zupancic, and M. Thomas Record, Jr. OLV

BTW, transcription isn’t simple either. OLV

“This discovery was made by developing a type of advanced microscopy that directly visualizes the translation of the genetic code in a living cell.” That’s not a code. ;) OLV

Such a complexity is just an illusion. ;) It ain’t real. OLV

We keep learning about a variety of life forms that they are “more complex than expected.” So why do we keep expecting them to be simpler? That’s a very intriguing question I would like to hear the answer for. OLV