7.342 Non-conventional Information Transfer in Biological Systems Fall 1999, Wednesdays 7:15-9:15 pm, 68-151
Harold J. Drabkin, Instructor, Rm. 4-253;
hdrabkin@mit.edu
The focus of this seminar will be an examination of information flow in biological systems. The central dogma of molecular biology states that information flows from DNA to RNA to protein. We will begin with an examination of the experimental foundation of this classical paradigm, which in its simplest case suggests a one-to-one correspondence between the sequence of bases in DNA and the sequence of amino acids in protein. We will then discuss examples in which the final protein products do not correspond to the amino acid sequences predicted from the codons in the DNA. Topics will include RNA splicing, RNA editing, frame shifting, and protein splicing.
Course Requirements: This course is graded pass/fail. Attendance and in-class participation are essential. Missing more than two sessions will result in an immediate drop. The instructor must be notified a day in advance for an absence. During each meeting, two papers from the primary literature will be discussed in depth. Emphasis will be placed upon a clear understanding of methods, results, and conclusions. Each student will present and discuss scientific figures from assigned papers.
Additionally, two
written papers will be required. The first paper will be
due on either Oct. 13 or 20; the second one will be due the last
day of class (December 8). On December 8, each student will
present a topic to the class. The topics for the papers and class
will be on selected topics to be
assigned.
| Week of | Topic | Paper |
| Sept. 8 | Course
outline and requirements How to read a scientific
paper Review of central dogma |
Reading a scientific paper Case Western Biochemistry Biochem. 371 How to read a scientific paper |
| Sept. 15 | Co-linearity of Gene and Protein | Yanofsky,
C., Carlton, BC, Guest, JR, Lelinski, DR, and Henning, V
(1964). On the colinearity of gene structure and protein
structure. Proc. Natl. Acad. Sci. 51, 266 Sarabhai, Stretton and Brenner. (1964) Co-linearity of the gene with the polypeptide chain. Nature 201, 13-17 |
| Sept. 22 | RNA splicing: the first discoveries | Berget,
SM, Moore, C, and Sharp, PA (1977). Spliced segments at
the 5’ terminus of adenovirus 2 late mRNA. Proc.
Natl. Acad. Sci 74, 3171-3715 Mandel, et al. (1978). Organization of coding and intervening sequences in the chicken ovalbumin split gene. Cell 14:641-53. |
| Sept. 29 | Transsplicing: Protozoa | Sutton
RE, Boothroyd JC (1986) Evidence for trans splicing in
trypanosomes Cell 47(4): 527-35 Cell; 47(4):
517-25 Spieth J, Brooke G et al.(1993). Operons in C. elegans: polycistronic mRNA precursors are processed by trans-splicing of SL2 to downstream coding regions. Cell; 73:521-32 |
| Oct. 6 | Transsplicing: Mammals | Kanno,
H., I. -Y. Huang, Y. W. Kan, and A. Yoshida. (1989). Two
structural genes on different chromosomes are required
for encoding the major subunit of human red cell
glucose-6-phosphate dehydrogenase. Cell 58:595-606; BUT,
see also Yoshida, A., and Y. W. Kan. 1990. Origin of
"fused"glucose-6-phosphate dehydrogenase. Cell
62:7-12. Bo-Liang Li, et al. (1999) Human Acyl-CoA: Cholesterol Acyltransferase-1 (ACAT-1) Gene Organization and Evidence That the 4.3-Kilobase ACAT-1 mRNA Is Produced from Two Different Chromosomes J. Biol. Chem 274, 11060?11071, |
| Oct. 13 | tmRNA | Tu,
Guo-F., G. E. Reid, Jian-G. Zhang, R. L. Moritz, and R.
J. Simpson. 1995. C-terminal extension of truncated
recombinant proteins in Escherichia coli with a
10Sa RNA decapeptide. J. Biol. Chem. 270:9322-9326 Keiler, K. C., P. R. H. Waller, and R. T. Sauer. 1996. Role of a peptide tagging system in degradation of proteins synthesized from damaged messenger RNA |
| Oct. 20 | RNA editing I: base changes | Powell
et al. (1987) A novel form of tissue-specific RNA
processing produces apolipoprotein B48 in intestine. Cell
50, 831-840 Sommer, B.; Koehler, M.; Sprengel, R.; Seeburg, P. H. (1991) RNA editing in brain controls a determinant of ion flow in glutamate-gated * channels. Cell 67, 11-19 |
| Oct. 27 | RNA editing II: Additions and Insertions | Simpson,
L.; Shaw, J. (1989) RNA editing and the
mitochondrial cryptogenes of kinetoplastid
protozoa. Cell 57, 355-366 Shaw, J. M.; Feagin, J. E.; Stuart, K.; Simpson, L. (1988) Editing of kinetoplastid mitochondrial mRNAs by uridine addition and deletion generates conserved amino acid sequences and AUG initiation codons. Cell 53, 401-411 |
| Nov. 3 | RNA editing III Mechanism | Blum,
B., Sturm, N.R., Simpson, A.M. and Simpson, L. (1991)
Chimeric gRNA-mRNA molecules with oligo(U) tails
covalently linked at sites of RNA editing suggest that U
addition occurs by transesterification. Cell
65, 543-550 Sturm, N. R.; Simpson, L. (1990) Partially edited mRNAs for cytochrome b and subunit III of cytochrome oxidase from Leishmania tarentolae_ mitochondria: RNA editing intermediates. Cell 61, 871-878. |
| Nov. 10 | Frame shifting and Ribosome Hopping | Huang
WM,et al. (1988) A persistent untranslated sequence
within bacteriophage T4 DNA topoisomerase gene 60 Science
1988 239:1005-12. frame shifting paper to be assigned |
| Nov. 17 | Protein Splicing I: | 1.
Bowles, et al. (1986) J. Cell Bio. 102, 1284-1297.
Post-translational processing of concanavalin A
precursors in Jackbean cotyledons. See also the
summary by Sharon and Lis, in Nature 323, 203-204 (1986). 2. Carrington, Auffret, and Hanks (1985) Nature 313, 64-67. Polypeptide ligation occurs during post-translational modification of concanavalin A. See also summary by Gatehouse and Boulter, Nature 313, 13 (1985). |
| Nov. 24 | Thanksgiving Break | |
| Dec. 1 | Protein Splicing II | Xu,
M.-Q. et al. (1993). In vitro protein splicing off
purified precursor and the identification of a branched
intermediate. Cell 75, 1371-1377 Nogami, S. et al. (1997). Probing novel elements for protein splicing in the yeast VmaI protozyme: a study of replacement mutagenesis and intragenic suppression. Genetics 147, 73-85 |
| Dec. 8 | Last Class:2nd Paper Due | Oral Presentations |