Aims

Our understanding of how gene expression is regulated has improved enormously over recent years, and it is now appreciated that the amount of each gene product produced is determined by both transcription and post-transcriptional events up to RNA degradation, which may be generic or specific to some or even individual genes. This module will build on information received by students in the first and second years, developing appreciation of the biochemistry of core aspects of gene expression and its regulation at various levels, and introduce students to original literature associated with the field. The module also aims to develop core skills including data interpretation and exam essay skills.

Outline Of Syllabus

The core module lectures will cover key features of gene expression and associated biochemistry. Topics will be:

1) Overview of the module

2) DNA-dependent RNA polymerases. These enzymes are responsible for the first step in expression of information in our genes – generation of the pre-mRNA transcript. Structure and mechanism of DNA-dependent RNA polymerases, key features of eukaryotic RNA pol II, and particularly the C-terminal domain (CTD) of its largest subunit with which it interacts with many factors including the RNA processing machinery.

3) RNA polymerases are highly sensitive to local chromatin conformation, and both the mechanisms for modulating chromatin structure and the regulation of nucleosome dynamics during transcription will be discussed. Gene expression is also affected by methylation of DNA and mechanisms and consequences of this epigenetic modification to DNA will be discussed.

4) The production of mature mRNA via capping, splicing, polyadenylation and editing will be discussed, as will mRNA export form the nucleus. Alternative patterns of splicing, as well as the position of transcription initiation and polyadenylation, yield a huge diversity to the products of gene expression. The importance, mechanisms and regulation of alternative transcript processing will be discussed, as will the links between transcription, RNA processing and downstream events in RNA metabolism.

5) Mechanism and regulation of protein synthesis. Regulation of translation is a much more rapid response than changing transcription patterns, providing cells with a primary response to changing environment: key translational regulatory mechanisms and pathways will be discussed, as will the various pathways through which mRNAs are degraded.
     
6) Non-coding RNAs and ribonucleoproteins (RNPs) play key roles in the cell that extend beyond the standard gene expression pathway, and the importance of these will be discussed.

Complementing the core lectures, a research lecture and a seminar will form the remainder of the taught material. Both of these will be used to enhance the material in lectures, with examples of current research being discussed in the research lecture, and topics related to the course forming the material to be discussed in the seminar.

Teaching Rationale And Relationship

Lecture materials introduce the material on the course, delivering the bulk of the key knowledge required, so that students can meet the learning outcomes.

Skills practice sessions are generic, used to support development of core analytical and numerical skills across the curriculum.

Research Seminar workshops will expand on the material presented in lectures and also provide students with the opportunity to practise their critical and analytical skills further. The first session of the course (Introductory Workshop) will include information on the in-course assessments, including the Graphical Abstract and Highlights exercise.

Assessment Rationale And Relationship

The essay assesses each student’s knowledge base, comprehension and ability to discuss the subject critically.

The professional skills exercise is designed to test the student’s ability to distil key knowledge from a document (a research paper) into both pictorial (graphical abstract) and written (bullet point) form.