RNA Modifications Regulate Gene Expression During Development

RNA plays a critical role in gene expression within the cellular environment. Both messenger RNA (mRNA) and transfer RNA (tRNA) are involved in translating the instructions encoded in the DNA sequence of expressed genes into the manufacture of protein products at the site of the ribosomes. This process is, of course, happening continually throughout the life cycle of the cell. In the development of the human embryo in utero, the timing and orchestration of gene expression is vitally important; the precision of these processes is an absolute requirement for the successful creation of a viable individual at birth. The timed expression of development-related genes is determined by gene expression programs.

There is current evidence that there are modifications of RNA that function as post-transcriptional regulators of these gene expression programs. These regulators apparently impact a wide variety of eukaryotic biological processes. Michaela Frye from the Department of Genetics at the University of Cambridge, UK and her scientific collaborators stated in a recent article in the publication, Science, that “N6-methyladenosine affects the translation and stability of the modified transcripts, thus providing a mechanism to coordinate the regulation of groups of transcripts during cell state maintenance and transition. Similarly, some modifications in transfer RNAs are essential for RNA structure and function. Others are deposited in response to external cues and adapt global protein synthesis and gene-specific translation accordingly and thereby facilitate proper development.”

N6-methyladenosine

Gene expression in multicellular organisms is determined by a complex set of interacting and dynamic processes that require the coordination of mRNA metabolism and protein synthesis. There has been considerable investigation into the mechanism of transcriptional networks related to tissue-specific stem cell differentiation. However, the regulation of gene expression programs during development is especially crucial and must be unerringly precise. The recent evidence points to specific modifications of RNA as crucial to the regulation of cellular transcriptomes and proteomes during development.

At present there are over 170 modifications in RNA reported, but it is only following the relatively recent development of precise analytical tools that these modifications can be identified and quantified with precision. In addition to the N6 methyladenosine modification of mRNA as a crucial regulator of gene expression, other modifications including 5-methylcytosine and N1-methyladenosine are involved in the modification of both noncoding RNA and mRNA.

A detailed examination of some of these changes has been reported in the Science publication authored by Michaela Frye as noted above. These findings help to elucidate the molecular and cellular mechanisms that are involved in the intricate process of development.