David Bartel

Question

Why are some mRNAs much more long-lived than others or translated much better than others, and how do these differences in post-transcriptional gene regulation influence cellular function and development?  

Approach

mRNAs from different genes can have very different rates of decay or very different efficiencies of translation, and these differences can have profound effects on the amount of each protein produced by each cell. The Bartel lab uses innovative high-throughput biochemical and molecular analyses, together with computational and evolutionary approaches to gain initial insight into these gene-regulatory processes and generate new hypotheses. They then follow up on these insights with genetic, molecular, and in-depth biochemical analyses designed to elucidate molecular mechanisms.  

Bartel has a longstanding interest in microRNAs, which are short RNAs that interact with sites in mRNAs to direct the destabilization or translational repression of these targeted transcripts. The Bartel lab helped to define this class of small regulatory RNAs, their mRNA targets, and the molecular consequences of their action. For example, they and their collaborators showed that most human mRNAs are regulated by microRNAs. The lab is currently generating millions of affinity measurements that are revealing unanticipated differences between different microRNAs and providing information required to improve predictions of microRNA regulatory interactions. The lab is also turning its attention from how microRNAs are produced by the cell to how certain microRNAs are destroyed in a process that helps to shape the levels of different microRNAs in different cell types. This process is highjacked by some viruses, which use it to eliminate microRNAs that would otherwise impede viral replication.

In other experiments, the lab studies mRNAs, with emphasis on how mRNA structure, mRNA untranslated regions, and mRNA poly(A) tails recruit and mediate regulatory phenomena.  For example, they are learning why in early embryos mRNAs with shorter tails are translated less efficiently than those with longer tails, whereas later in development mRNAs with shorter tails are no longer less efficiently translated and instead are more rapidly degraded. The lab is also studying a recently discovered regulatory function for excised introns, which are RNA regions that are normally removed from mRNAs and then rapidly destroyed.
 

Bio

Bartel earned his bachelor’s degree in biology from Goshen College in 1982 and his Ph.D. degree in Virology from Harvard University in 1993, under the mentorship of Jack W. Szostak. Bartel joined Whitehead Institute in 1994 as a Whitehead Fellow. In 1996, he was appointed an Associate Member of Whitehead and assistant professor of biology at MIT. Bartel is now a Howard Hughes Medical Institute Investigator, a Member at Whitehead, and professor at MIT.