Course Organiser: Michelle West (JMS 3C20)

Regulating the Transcriptome

Course code: C7132

AUTUMN 2010

Course Organiser: Michelle West (JMS 3C20)

Course description

The transcriptome is the set of all messenger RNA (mRNA) molecules produced in a cell, cell-type or organism. The production and processing of mRNA molecules is highly regulated particularly at the levels of transcription and splicing (in eukaryotes). This regulation is crucial to enable gene expression to be finely tuned and to respond to environmental cues.

This course takes an in-depth look at the molecular mechanisms controlling RNA expression in prokaryotes and eukaryotes focussing largely on gene transcription but also examining RNA processing events. General topics covered include:

• The structure, function and regulation of RNA polymerases, activators and repressors.
• How transcription is regulated in response to stress in bacteria.
• Coactivators/corepressors and chromatin modifications.
• Processing transcripts through capping, polyadenylation and splicing.

Both lecturers on the course are active researchers in the subject areas covered and will provide a fully up-to-date overview of an active and interesting research area that is relevant to the fundamental understanding of living cells. The processes and mechanisms covered provide vital information relevant to health and disease e.g. antibiotic-producing bacteria, human genetic diseases and cancer.

Lecturers: Mark Paget and Michelle West.
Teaching and learning:

There will be up to 3 teaching sessions per week.

1 lecture in weeks 1 and 10

2 lectures per week in weeks 2 and 6

2 lectures per week plus one seminar in weeks 3, 4, 5, 7, 8 and 9.

All sessions including seminars are compulsory. Attendance will be recorded at seminars in accordance with university rules.

Lectures
Lectures will be used to explain the main theoretical concepts in the field, together with experimental approaches, and illustrate these with specific examples. A major function of the lectures is to provide a framework for your own reading using the specialised reading lists for each topic. You should note that final year lectures each contain a substantial amount of material, and that most of them constitute part of a series developing a particular topic. Thus, missingeven a single lecture will involve you in a great deal of extra time retrieving the lost material, and will also impair your ability to understand the material in the subsequent lectures in the series. You are therefore advised to attend EVERY lecture unless prevented from doing so by illness.

Slides, lecture notes and reading lists will be provided on Study Direct.

Please note that at this level the lectures on their own cannot provide the comprehensive coverage of the topic that you are expected to obtain to be able to provide full and complete answers to exam questions. Supplementing lecture material through your own reading is a critical part of the learning process.

Active teaching and learning

Ongoing question and answer during lectures will enable you to engage with the topic and relate it to your previous knowledge.

Time will be made available for specific discussion in groups at the end of lectures.

You will be expected to post one or more questions that arise in your groups on the online discussion forum on study direct and to engage in discussion with your peers.

You are also encouraged to use the forum to post any useful/helpful further resources e.g. papers and websites.

You will benefit from formative feedback through the discussion forum, in class discussions and during seminar session discussions.

Reading lists
Textbooks do not cover extensive amounts of the content of this course in sufficient depth to be relied on for more than a general introduction to most topics. In addition, the rapid development of knowledge in this area means that even recent textbooks lack important new information. The lecturers will include some textbooks on their reading lists and advise of the lectures/areas that they may be useful for.

Most of your reading will be of reviews in research journals and some research papers. Reading lists will be given out at the lectures and are available on study direct.

When you use the detailed reference lists provided at the lectures the lists may look long and daunting. Don’t panic! The relatively smaller numbers of critical references are highlighted, and the others are there for you to further broaden your knowledge.

Learning outcomes

By the end of the course, a successful student should be able to:

1.Describe the factors and molecular mechanisms involved in the regulation of transcription and processing.

2.Compare and contrast the mechanisms involved in controlling prokaryotic and eukaryotic RNA expression.

3.Utilise information extracted from the relevant scientific literature.

4.Describe key scientific techniques used to study transcription and processing and interpret and analyse data obtained using these techniques.

Topics covered

Prokaryotic transcription (Mark Paget)

•Structure and function of prokaryotic polymerase.

•The recognition of promoter DNA sequences by transcription factors.

•Transcriptional activation and repression mechanisms.

•Alternative sigma factors.

•The regulation of transcription during stress responses (heat shock, oxidative stress and nutrient limitation).

•Seminars will focus on the techniques used to investigate transcription.

Eukaryotic transcription (Michelle West)

•Structure and function of eukaryotic RNA polymerase II.

• Eukaryotic initiation and elongation and their regulation by general initiation and elongation factors and specific activator and repressor proteins.

• The role of coactivators and corepressors in the regulation of chromatin structure during transcription.

• Processing mechanisms and the coupling of transcription to RNA processing.

• Seminars will focus on techniques used to investigate eukaryotic transcription.

Assessment

Please see Sussex Direct for details on assessment.

This course was new in 2009 so only one past paper will be available.

However, the content of this course previously formed part of a 30 credit course called’ Biochemistry of Gene Expression’. Past papers from this course are available and may be consulted for some idea of exam question style and content, as many of the topics covered remain the same. You should note however that this was a longer exam and also covered additional topics no longer covered in this course. Please consult the lecturers if you are in any doubt about past exam questions and their relevance.

Plagiarism

The issue of plagiarism is a growing academic concern, and one that the University of Sussex takes seriously. Up to date information on the University regulations concerning plagiarism can be found at the following link:

Student feedback
Student feedback will be monitored by an end-of-term questionnaire that must be completed online. PLEASE FILL IN THE QUESTIONNAIRE-your comments on the course are very valuable. We welcome suggestions for improvements for future years as well as positive feedback.

The response rate using online evaluation last year was poor. Nonetheless, of the 10/33 students that filled in the form, all rated all aspects of the course very highly, with all relevant questions on teaching quality, self development and motivation, course organisation and learning resources receiving mean scores ranging from 4.3 to 4.8 out of 5. Informal feedback (the only form of feedback possible in this course) was rated at 4.6, with an overall course quality score of 4.5. A number of students made very positive comments about the excellent and high-standard of teaching, up-to-date lectures and enthusiasm of lecturers. The seminars were well received, with 4 students commenting on their usefulness instimulating interest and engagement.

Suggestions for improvement were few, but included expanding on the methods covered in seminars in lectures and making group work for seminars optional. Group work is an important life skill and we will continue to encourage this on the course this yearbut will expand the detail given on methods in response to these comments.

Regulating the Transcriptome- timetable

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