The information for creating proteins is stored in cells in the form of DNA, but the genome remains a useless blueprint without transcription into messenger RNA molecules (mRNAs) and other, less well understood long noncoding RNAs (lncRNAs). This process is subjected to extensive regulatory processes, which are critical in order to ensure precise expression of the specific repertoire of proteins establishing cell-type–specific identity. Some of the most fascinating forms of regulation are applied to mRNA following transcription, and these have dramatic effects on the identity and the quantity of the protein that will eventually be produced. These regulatory pathways have not only been implicated as the molecular mechanisms underlying multiple human diseases, but are also increasingly adopted as a strategy for therapeutic intervention. In this course we will explore all the major points of control during the life trajectory of an mRNA, and discuss the functional outcomes of their impairment. Topics will include splicing, polyadenylation, export from the nucleus, localization to cellular bodies, translation, and decay. We will also discuss RNAi and its therapeutic uses, and long noncoding RNAs that do no encode proteins. We will learn about both traditional and cutting edge approaches for studying the transcriptome at different resolutions, as well as computational and statistical methods for interpreting the data they generate. Emphasis will be put on designing and critically interpreting experiments.
We expect to cover the following topics (typically one topic a week):
- Constitutive and alternative splicing
- Determination of 3' ends by cleavage and polyadenylation
- Export from nucleus to cytosol
- mRNA degradation
- Nonsense mediated decay
- mRNA localization in the cytoplasm
- Translational control
- RNA interference
- RNA editing and other modifications
- Long noncoding RNAs and their deviations from mRNAs
- Circular RNAs
- Processing of long RNAs into microRNAs and other small RNAs