Course Meeting Times
Lectures: 1 session / week, 2 hours / session
Prerequisites
Recommended prerequisites for this course are one of the following:
7.06 Cell Biology
7.28 Molecular Biology
Course Description
While most cells in the body have exactly the same DNA, cells differ drastically in how they use their DNA. RNA, which is transcribed from DNA, is front and center of this specificity of expression and regulation of genetic information. This course will explore the current frontiers of the world of RNA biology with primary research papers to trace how the original odd detail sometimes leads to major discoveries.
We will explore the unexpected diversity of RNA classes and the mechanisms by which they are generated and exert their function. For example, while DNA base-pairing is mainly used to replicate genetic information, RNAs employ base-pairing for a wider array of functions, including specific binding to other RNAs.
We will first review and update our knowledge about the historically best characterized RNAs: messenger RNA (mRNA), transfer RNA, and ribosomal RNA, which together employ basepairing to read the genetic code and synthesize proteins. In many organisms messenger RNAs undergo a processing step called splicing, which allows for many alternative variant messages to be made from the same gene and explains how the human body can make over 100,000 proteins from only 20,000 genes.
On our field trip, we will visit Arrakis Therapeutics and learn about their approach to discovering RNA-targeted small molecules (rSMs) in order to develop drugs for treating diseases. We will then turn to more recently discovered small noncoding RNAs, such as microRNAs, siRNAs, and piRNAs, which regulate the functions of other genes and can change the fate of cell types during development.
Finally, we will discuss other RNA species about which we still know very little, such as long non-coding RNAs and circular RNAs. Some long noncoding RNAs associate with chromatin, thereby altering the expression of other genes or bringing together different chromosomes in the nucleus. Circular RNAs are unexpected products of splicing, which have no ends and are therefore very stable compared to other RNAs. While many of them are probably by-products, some exist in surprisingly large quantities. These can alter regulation by microRNAs or RNA-binding proteins, in one example with very specific consequences on behavior. Some circRNA have the capacity to be translated and make small proteins, adding to the already vast protein diversity enabled by alternative splicing. As we discuss the different transcripts and processing events that enable this exciting diversity of RNA functions, we invite you to read landmark papers with us, think critically, and ask new questions, as we marvel at the wonders of RNA.
Format
Our class will meet weekly for two hours. Each week we will discuss two primary research papers from the scientific literature. Students will read these papers before each class and are expected to prepare two questions or comments per paper for the ensuing discussion (e.g., “Why did they do this experiment?” or “I don’t feel they can conclude this from this Figure”).
At the beginning of each class, students will briefly summarize the first paper, then walk through the main figures and tables of the paper. Questions (including the submitted questions) will be raised during the presentation and discussed by the entire class. Updates from more recent research will be inserted when it makes sense. Then the second paper will be similarly discussed. At the end of each class, instructors will provide background necessary to understand the rationale and experiments of the papers to be discussed in the following week’s session.
Initially, students will be helped in discussion by the instructors, but for the later sections of the course, students will be expected to form their own arguments that support or challenge key conclusions of the papers. Discussions will revolve around critically evaluating the rationale supporting the experiments performed, the experimental study design, properly controlled experiments, and the support for the conclusions drawn based on the data. Students are expected to be the main contributors of the discussion of every class with critical thinking.
Requirements
- Students are required to attend every class and participate in the discussion
- Written assignment due on week 7 at the beginning of the class
- Oral presentation/lead of discussion of one paper of choice at week 13
Grading
The course will be graded as “pass” or “fail.” A passing grade will be given to students who attend the class, participate appropriately in discussions, and complete both written and oral assignments in a satisfactory manner.
Calendar
| week # | topics | key dates |
|---|---|---|
| 1 | Overview | |
| 2 | From the discovery of mRNA to the “central dogma” | |
| 3 | From the discovery of splicing to studying entire “transcriptomes” | |
| 4 | What is a gene really? From baby RNAs to mature mRNAs | Abstracts handed out for written assignment |
| 5 | How mRNAs are synthesized | |
| 6 | How you start is how you proceed: promoter control of alternative splicing and processing | |
| 7 | miRNAs: small RNAs making a big splash | Written assignment due |
| 8 | Field trip to Arrakis Therapeutics | |
| 9 | siRNAs: How silencing almost any gene became easy and cheap | |
| 10 | It’s after the stop, yet somehow on top. How the 3’UTR regulates the function of encoded proteins | |
| 11 | Raise the shields (and scissors)! piRNA and CRISPR are defensive RNA-weapon systems | |
| 12 | Easy to miss, hard to degrade: circular RNA and lncRNAs | |
| 13 | Integration of classes, writing assignment, and course discussion | Oral presentation due |
