A pinboard by
Boxuan Zhao

Graduate Student, University of Chicago


Tiny modifications on RNA have huge impacts on biological processes!

Over 100 types of chemical modifications exist on RNA and carry out distinct functions. Among these RNA modifications, m6A is the most abundant epigenetic mark on mRNA and plays critical regulatory roles in RNA metabolism. Functioning through specific reader proteins, m6A notably increases mRNA translation efficiency or accelerates the decay of marked transcripts, both critical for the change of gene expression profile and cell state. However, the involvement of m6A in complex biological processes is largely unknown. My research has been primarily focused on the investigation of biological functions of m6A. Using both model organisms and human samples, we have discovered several physiological systems that m6A plays essential roles in, which include embryo development and viral infection. During vertebrate embryogenesis, there is a rapid clearance of mRNA during early phase, which we propose to be facilitated by m6A. Our study of zebrafish embryogenesis showed that over one-third of zebrafish maternal mRNA can be marked by m6A, and the clearance of these maternal mRNAs is facilitated by an m6A reader protein Ythdf2, which confirmed m6A-dependent RNA decay as a key regulator of animal development. In the case of viral infection, RNA is used by many viruses as the vital genetic material and may be subjected to m6A regulation. Using HIV as the model system, we have generated the high-resolution m6A map of HIV and discovered that the perturbation of m6A regulators will impact the efficiency of HIV infection and replication. Host m6A readers negatively impact viral infection through the inhibition of viral reverse transcription, which suggest viral infection is highly regulated by m6A mechanisms. These findings highlighted the critical roles of m6A mRNA methylation in complex biological processes and more functions may remain to be discovered.


The RNA Modification N(6)-methyladenosine and Its Implications in Human Disease.

Abstract: Impaired gene regulation lies at the heart of many disorders, including developmental diseases and cancer. Furthermore, the molecular pathways that control gene expression are often the target of cellular parasites, such as viruses. Gene expression is controlled through multiple mechanisms that are coordinated to ensure the proper and timely expression of each gene. Many of these mechanisms target the life cycle of the RNA molecule, from transcription to translation. Recently, another layer of regulation at the RNA level involving RNA modifications has gained renewed interest of the scientific community. The discovery that N(6)-methyladenosine (m(6)A), a modification present in mRNAs and long noncoding RNAs, can be removed by the activity of RNA demethylases, launched the field of epitranscriptomics; the study of how RNA function is regulated through the addition or removal of post-transcriptional modifications, similar to strategies used to regulate gene expression at the DNA and protein level. The abundance of RNA post-transcriptional modifications is determined by the activity of writer complexes (methylase) and eraser (RNA demethylase) proteins. Subsequently, the effects of RNA modifications materialize as changes in RNA structure and/or modulation of interactions between the modified RNA and RNA binding proteins or regulatory RNAs. Disruption of these pathways impairs gene expression and cellular function. This review focuses on the links between the RNA modification m(6)A and its implications in human diseases.

Pub.: 24 May '17, Pinned: 28 Jun '17