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7.341 | Spring 2019 | Undergraduate

# DNA's Sister Does All the Work: The Central Roles of RNA in Gene Expression

week # | topics | readings
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1 | Overview See the Lecture Summary | Jacob F & Monod J. (1961) Genetic regulatory mechanisms in the synthesis of proteins. Journal of Molecular Biology. 3(3): 318-356.

2 | From the discovery of mRNA to the “central dogma” See the Lecture Summary | Astrachan L & Volkin E. (1958) Properties of ribonucleic acid turnover in T2-infected Escherichia coli. Biochemica et Biophysica Acta. 29: 536-544. Brenner S, Jacob F, Meselson M. (1961) An unstable intermediate carrying information from genes to ribosomes for protein synthesis. Nature. 190: 576-581.

3 | From the discovery of splicing to studying entire “transcriptomes” See the Lecture Summary | Berget S M, Moore C, Sharp P A. (1977) Spliced segments at the 5′ terminus of adenovirus 2 late mRNA. Proceedings of the National Academy of Sciences of the United States of America. 74(8): 3171–3175. Nagalakshmi U, Wang Z, Waern K, Shou C, Raha D, Gerstein M, Snyder M. (2008) The transcriptional landscape of the yeast genome defined by RNA sequencing. Science. 320(5881): 1344-1349.

4 | What is a gene really? From baby RNAs to mature mRNAs See the Lecture Summary | Merkin J, Russell C, Chen P, Burge CB. (2012) Evolutionary dynamics of gene and isoform regulation in mammalian tissues. Science. 338(6114): 1593-1599. de la Mata M, Alonso CR, Kadener S, Fededa JP, Blaustein M, Pelisch F, Cramer P, Bentley D, Kornblihtt AR.(2003) A slow RNA polymerase II affects alternative splicing in vivo. Molecular Cell. 12(2): 525-532.

5 | How mRNAs are synthesized See the Lecture Summary | Schor IE, Degner JF, Harnett D, Cannavò E, Casale FP, Shim H, Garfield DA, Birney E, Stephens M, Stegle O, Furlong EE. (2017) Promoter shape varies across populations and affects promoter evolution and expression noise. Nature Genetics. 49(4): 550-558. Duttke SHC, Lacadie SA, Ibrahim MM, Glass CK, Corcoran DL, Benner C, Heinz S, Kadonaga JT, Ohler U. (2015) Human promoters are intrinsically directional. Molecular Cell. 57(4): 674-684.

6 | How you start is how you proceed: promoter control of alternative splicing and processing See the Lecture Summary | Cramer P, Pesce CG, Baralle FE, Kornblihtt AR. (1997) Functional association between promoter structure and transcript alternative splicing. Proceedings of the National Academy of Sciences of the United States of America. 94(21): 11456-11460. Chen Y, Pai AA, Herudek J, Lubas M, Meola N, Järvelin AI, Andersson R, Pelechano V, Steinmetz LM, Jensen TH, Sandelin A. (2016) Principles for RNA metabolism and alternative transcription initiation within closely spaced promoters. Nature Genetics. 48(9): 984-994.

7 | miRNAs: small RNAs making a big splash See the Lecture Summary | Lee RC, Feinbaum RL, Ambros V. (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 75(5): 843-854. Flamand MN, Gan HH, Mayya VK, Gunsalus KC, Duchaine TF. (2017) A non-canonical site reveals the cooperative mechanisms of microRNA-mediated silencing. Nucleic Acids Research. 45(12): 7212-7225.

8 | Field trip to Arrakis Therapeutics See the Lecture Summary | Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F, Ebina W, Mandal PK, Smith ZD, Meissner A, Daley GQ, Brack AS, Collins JJ, Cowan C, Schlaeger TM, Rossi DJ. (2010) Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell. 7(5): 618-630.

9 | siRNAs: How silencing almost any gene became easy and cheap See the Lecture Summary | Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 391(6669): 806-811. Jenal M, Elkon R, Loayza-Puch F, van Haaften G, Kühn U, Menzies FM, Oude Vrielink JA, Bos AJ, Drost J, Rooijers K, Rubinsztein DC, Agami R. (2012) The poly(A)-binding protein nuclear 1 suppresses alternative cleavage and polyadenylation sites. Cell. 149(3): 538-553.

10 | It’s after the stop, yet somehow on top. How the 3’UTR regulates the function of encoded proteins See the Lecture Summary | Kristjánsdóttir K, Fogarty EA, Grimson A. (2015) Systematic analysis of the Hmga2 3′ UTR identifies many independent regulatory sequences and a novel interaction between distal sites. RNA. 21(7): 1346-1360. Berkovits BD, Mayr C. (2015) Alternative 3’ UTRs act as scaffolds to regulate membrane protein localization. Nature. 522(7556): 363-367.

11 | Raise the shields (and scissors)! piRNA and CRISPR are defensive RNA-weapon systems See the Lecture Summary | Brennecke J, Aravin AA, Stark A, Dus M, Kellis M, Sachidanandam R, Hannon GJ. (2007) Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell. 128(6): 1089-1103. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. (2012) A programmable dual-RNA–guided DNA endonuclease in adaptive bacterial immunity. Science. 337(6096): 816-821.

12 | Easy to miss, hard to degrade: circular RNA and lncRNAs See the Lecture Summary | Piwecka M, Glažar P, Hernandez-Miranda LR, Memczak S, Wolf SA, Rybak-Wolf A, Filipchyk A, Klironomos F, Cerda Jara CA, Fenske P, Trimbuch T, Zywitza V, Plass M, Schreyer L, Ayoub S, Kocks C, Kühn R, Rosenmund C, Birchmeier C, Rajewsky N. (2017) Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function. Science. 357(6357): eaam8526. Chaumeil J, Le Baccon P, Wutz A, Heard E. (2006) A novel role for Xist RNA in the formation of a repressive nuclear compartment into which genes are recruited when silenced. Genes & Development. 20(16): 2223-2237.

13 | Integration of classes, writing assignment, and course discussion See the Lecture Summary | No Readings

## Course Info

##### Instructors

- Dr. Ana Fiszbein
- Dr. Marvin Jens

##### Departments

- Biology

##### As Taught In

Spring 2019

##### Level

Undergraduate

##### Topics

- Engineering
  - Biological Engineering
    - Biotechnology
- Science
  - Biology
    - Genetics
    - Molecular Biology

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