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Regulation of Protein Synthesis by mRNA Structure

Project Collaborators:

Dr. Gloria Culver, Dr. David Mathews

Illustration of mRNA folding using single-molecule FRET

Experimental design for the detection of mRNA folding using single-molecule FRET. Donor
and acceptor fluorophores are shown by green and red respectively. A biotin-labeled DNA
oligo is used for the immobilization of fluorescently-labeled mRNA in fluorescent
single-molecule microscopy imaging.

The central dogma of Biology is that DNA is used to make messenger RNA (mRNA), which is used to make proteins. Over the last decade, multiple findings have illuminated the importance of the regulation of protein expression at the level of mRNA translation. mRNA is no longer considered a simple courier of genetic information between DNA and protein. RNA can fold into an extensive secondary and, in many instances, tertiary structure.

In recent years, numerous studies began to reveal that structured elements within the mRNA play a critical role in modulating the flow of genetic information from DNA to protein. For example, structured RNA elements located within the 5’ untranslated regions of bacterial mRNAs (called riboswitches) can regulate transcription elongation and translation initiation by sensing the presence of various metabolites whose binding to RNA results in the stabilization of one of the alternative structures of RNA. Likewise, in eukaryotes, structured regions of mRNA were shown to be responsible for regulating mRNA splicing, inducing programmed ribosomal frameshifting, and mediating cap-independent translation initiation via Internal Ribosome Entry Sites.

In our laboratory, we examine the effects of mRNA structure on protein synthesis. Our studies include investigations of bacterial riboswitches (in collaboration with Prof. Joseph Wedekind, University of Rochester), the stimulation of programmed ribosomal frameshifting by RNA structure and the role of mRNA structure in translation initiation in eukaryotes (in collaboration with Prof. David Mathews and Gloria Culver, both at the University of Rochester). We are also interested in the mechanism by which RNA helicases modulate mRNA structure and translation.

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