RNA Biology

E-mail: alex.stark(at)imp.ac.at
Phone: 0043 1 4277 79730
Research Group: www.imp.ac.at/groups/alexander-stark
Institution: Research Institute of Molecular Pathology (IMP)

Full member of the Focus Regulatory RNA (SFB RNA-REG) since 2011.
Full member of the DoktoratsKolleg (DK) RNA Biology since 2014.

PhD students within/associated to the DK RNA Biology:
Oliver HENDY
Leonid SEREBRENI

DK RNA Biology Alumni:
M. Mamduh A. ZABIDI: “Enhancer-responsiveness and -specificity of core promorters on gene transcription”

For complete list of group members please visit the Stark group website.

Joint research project J. Brennecke and A. Stark:

We propose to perform an unbiased study of RNA-abundance and post-transcriptional regulation in the female Drosophila germ line. Drosophila oogenesis serves as a paradigm for regulation of gene expression at the RNA-level, as all 3 known small RNA pathways (miRNAs, siRNAs, PiRNAs) are employed and it is the key system in which control of RNA localization, translation and transport have been established and are actively studied.

Specifically, we will establish and employ ribosome foot-printing (Ingolia et al. 2009) to determine ribosome occupancy and translation rates of mRNAs and RNA-PAR-CLIP (Hafner et al, 2010) to identify the specific target RNAs of three key protein factors involved in post-transcriptional regulation (Pumilio, Staufen, and Argonaute 1). We will couple these genom-wide approaches to bioninformatics analyses established in our or the Hofacker groups to determine the cis-regulatory motifs of RNAs at the level of sequence and secondary structure. We anticipate gaining significant insight into the post-transcriptional control of RNA fate in a complex in vivo context.

In a broader perspective, both technologies will proof extremely useful for the scientific progress within the Brennecke/Stark labs, which are focusing on small RNAs and cis-regulatory motifs. Finally, we believe that multiple groups within this SFB (e.g. Kiebler, Dorner, Mochizuki, Martinez) and a number of labs at the Vienna Biocenter Campus will benefit strongly from the establishment of the two technologies.

 

Publications: (since 2011)

Transcriptional cofactors display specificity for distinct types of core promoters.
Haberle V, Arnold CD, Pagani M, Rath M, Schernhuber K, Stark A.
Nature. 2019 Jun;570(7759):122-126

A high-throughput method to identify trans-activation domains within transcription factor sequences.
Arnold CD, Nemčko F, Woodfin AR, Wienerroither S, Vlasova A, Schleiffer A, Pagani M, Rath M, Stark A.
EMBO J. 2018 Aug 15;37(16).

Eukaryotic core promoters and the functional basis of transcription initiation.
Haberle V, Stark A.
Nat Rev Mol Cell Biol. 2018 Jun 26.

Assessing sufficiency and necessity of enhancer activities for gene expression and the mechanisms of transcription activation.
Catarino RR, Stark A.
Genes Dev. 2018 Feb 1;32(3-4):202-223.

Resolving systematic errors in widely used enhancer activity assays in human cells.
Muerdter F, Boryń ŁM, Woodfin AR, Neumayr C, Rath M, Zabidi MA, Pagani M, Haberle V, Kazmar T, Catarino RR, Schernhuber K, Arnold CD, Stark A.
Nat Methods. 2018 Feb;15(2):141-149.

A reversible haploid mouse embryonic stem cell biobank resource for functional genomics.
Elling U, Wimmer RA, Leibbrandt A, Burkard T, Michlits G, Leopoldi A, Micheler T, Abdeen D, Zhuk S, Aspalter IM, Handl C, Liebergesell J, Hubmann M, Husa AM, Kinzer M, Schuller N, Wetzel E, van de Loo N, Martinez JAZ, Estoppey D, Riedl R, Yang F, Fu B, Dechat T, Ivics Z, Agu CA, Bell O, Blaas D, Gerhardt H, Hoepfner D, Stark A, Penninger JM.
Nature. 2017 Oct 5;550(7674):114-118.

Promoting transcription over long distances.
Catarino RR, Neumayr C, Stark A.
Nat Genet. 2017 Jun 28;49(7):972-973.

Probing the canonicity of the Wnt/Wingless signaling pathway.
Franz A, Shlyueva D, Brunner E, Stark A, Basler K.
PLoS Genet. 2017 Apr 3;13(4):e1006700.

Combinatorial function of transcription factors and cofactors.
Reiter F, Wienerroither S, Stark A.
Curr Opin Genet Dev. 2017 Apr;43:73-81.

Genome-wide assessment of sequence-intrinsic enhancer responsiveness at single-base-pair resolution.
Arnold CD, Zabidi MA, Pagani M, Rath M, Schernhuber K, Kazmar T, Stark A.
Nat Biotechnol. 2017 Feb;35(2):136-144.

Regulatory Enhancer-Core-Promoter Communication via Transcription Factors and Cofactors.
Zabidi MA, Stark A.
Trends Genet. 2016 Dec;32(12):801-814.

RNA-binding profiles of Drosophila CPEB proteins Orb and Orb2.
Stepien BK, Oppitz C, Gerlach D, Dag U, Novatchkova M, Krüttner S, Stark A, Keleman K.
Proc Natl Acad Sci U S A. 2016 Oct 24.

Gene Regulation: Activation through Space.
Muerdter F, Stark A.
Curr Biol. 2016 Oct 10;26(19):R895-R898.

Genome-Wide Ultrabithorax Binding Analysis Reveals Highly Targeted Genomic Loci at Developmental Regulators and a Potential Connection to Polycomb-Mediated Regulation.
Shlyueva D, Meireles-Filho AC, Pagani M, Stark A.
PLoS One. 2016 Aug 30;11(8):e0161997.

Transcriptional regulators form diverse groups with context-dependent regulatory functions.
Stampfel G, Kazmar T, Frank O, Wienerroither S, Reiter F, Stark A.
Nature. 2015 Dec 3;528(7580):147-51.

Transcriptional plasticity promotes primary and acquired resistance to BET inhibition.
Rathert P, Roth M, Neumann T, Muerdter F, Roe JS, Muhar M, Deswal S, Cerny-Reiterer S, Peter B, Jude J, Hoffmann T, Boryń ŁM, Axelsson E, Schweifer N, Tontsch-Grunt U, Dow LE, Gianni D, Pearson M, Valent P, Stark A, Kraut N, Vakoc CR, Zuber J.
Nature. 2015 Sep 24;525(7570):543-547.

Coordinating the human looks.
Haberle V, Stark A.
Cell. 2015 Sep 24;163(1):24-6.

Enhancer-core-promoter specificity separates developmental and housekeeping gene regulation.
Zabidi MA, Arnold CD, Schernhuber K, Pagani M, Rath M, Frank O, Stark A.
Nature. 2015 Feb 26;518(7540):556-9.

The RNA-binding protein Arrest (Bruno) regulates alternative splicing to enable myofibril maturation in Drosophila flight muscle.
Spletter ML, Barz C, Yeroslaviz A, Schönbauer C, Ferreira IR, Sarov M, Gerlach D, Stark A, Habermann BH, Schnorrer F.
EMBO Rep. 2015 Feb;16(2):178-91.

Genomics: Hiding in plain sight.
Muerdter F, Stark A.
Nature. 2014 Aug 28;512(7515):374-5.

Genome-scale functional characterization of Drosophila developmental enhancers in vivo.
Kvon EZ, Kazmar T, Stampfel G, Yáñez-Cuna JO, Pagani M, Schernhuber K, Dickson BJ, Stark A.
Nature. 2014 Aug 7;512(7512):91-5.

Quantitative genome-wide enhancer activity maps for five Drosophila species show functional enhancer conservation and turnover during cis-regulatory evolution.
Arnold CD, Gerlach D, Spies D, Matts JA, Sytnikova YA, Pagani M, Lau NC, Stark A.
Nat Genet. 2014 Jul;46(7):685-92.

Dissection of thousands of cell type-specific enhancers identifies dinucleotide repeat motifs as general enhancer features.
Yáñez-Cuna JO, Arnold CD, Stampfel G, Boryń LM, Gerlach D, Rath M, Stark A.
Genome Res. 2014 Jul;24(7):1147-56.

Hormone-responsive enhancer-activity maps reveal predictive motifs, indirect repression, and targeting of closed chromatin.
Shlyueva D, Stelzer C, Gerlach D, Yáñez-Cuna JO, Rath M, Boryń ŁM, Arnold CD, Stark A.
Mol Cell. 2014 Apr 10;54(1):180-192.

Transcriptional enhancers: from properties to genome-wide predictions.
Shlyueva D, Stampfel G, Stark A.
Nat Rev Genet. 2014 Apr;15(4):272-86.

A conserved role for Snail as a potentiator of active transcription.
Rembold M, Ciglar L, Yáñez-Cuna JO, Zinzen RP, Girardot C, Jain A, Welte MA, Stark A, Leptin M, Furlong EE.
Genes Dev. 2014 Jan 15;28(2):167-81.

cis-regulatory requirements for tissue-specific programs of the circadian clock.
Meireles-Filho ACA, Bardet AF, Yáñez-Cuna JO, Stampfel G, Stark A.
Curr Biol. 2014 Jan 6;24(1):1-10.

Identification of transcription factor binding sites from ChIP-seq data at high resolution.
Bardet AF, Steinmann J, Bafna S, Knoblich JA, Zeitlinger J, Stark A.
Bioinformatics. 2013 Nov 1;29(21):2705-13.

Regulatory Genomics – Decoding Drosophila Regulatory Sequences.
Stark A.
Biomed Tech (Berl). 2013 Sep 7.

Genome-wide quantitative enhancer activity maps identified by STARR-seq.
Arnold CD, Gerlach D, Stelzer C, Boryń ŁM, Rath M, Stark A.
Science. 2013 Mar 1;339(6123):1074-7.

Deciphering the transcriptional cis-regulatory code.
Yáñez-Cuna JO, Kvon EZ, Stark A.
Trends Genet. 2013 Jan;29(1):11-22.

A histone deacetylase adjusts transcription kinetics at coding sequences during Candida albicans morphogenesis.
Hnisz D, Bardet AF, Nobile CJ, Petryshyn A, Glaser W, Schöck U, Stark A, Kuchler K.
PLoS Genet. 2012;8(12):e1003118.

Uncovering cis-regulatory sequence requirements for context-specific transcription factor binding.
Yáñez-Cuna JO, Dinh HQ, Kvon EZ, Shlyueva D, Stark A.
Genome Res. 2012 Oct;22(10):2018-30.

HOT regions function as patterned developmental enhancers and have a distinct cis-regulatory signature.
Kvon EZ, Stampfel G, Yáñez-Cuna JO, Dickson BJ, Stark A.
Genes Dev. 2012 May 1;26(9):908-13.

A computational pipeline for comparative ChIP-seq analyses.
Bardet AF, He Q, Zeitlinger J, Stark A.
Nat Protoc. 2011 Dec 15;7(1):45-61.

Forward and reverse genetics through derivation of haploid mouse embryonic stem cells.
Elling U, Taubenschmid J, Wirnsberger G, O’Malley R, Demers SP, Vanhaelen Q, Shukalyuk AI, Schmauss G, Schramek D, Schnuetgen F, von Melchner H, Ecker JR, Stanford WL, Zuber J, Stark A, Penninger JM.
Cell Stem Cell. 2011 Dec 2;9(6):563-74.

A high-resolution map of human evolutionary constraint using 29 mammals.
Lindblad-Toh K, Garber M, Zuk O, Lin MF, Parker BJ, Washietl S, Kheradpour P, Ernst J, Jordan G, Mauceli E, Ward LD, Lowe CB, Holloway AK, Clamp M, Gnerre S, Alföldi J, Beal K, Chang J, Clawson H, Cuff J, Di Palma F, Fitzgerald S, Flicek P, Guttman M, Hubisz MJ, Jaffe DB, Jungreis I, Kent WJ, Kostka D, Lara M, Martins AL, Massingham T, Moltke I, Raney BJ, Rasmussen MD, Robinson J, Stark A, Vilella AJ, Wen J, Xie X, Zody MC; Broad Institute Sequencing Platform and Whole Genome Assembly Team, Baldwin J, Bloom T, Chin CW, Heiman D, Nicol R, Nusbaum C, Young S, Wilkinson J, Worley KC, Kovar CL, Muzny DM, Gibbs RA; Baylor College of Medicine Human Genome Sequencing Center Sequencing Team, Cree A, Dihn HH, Fowler G, Jhangiani S, Joshi V, Lee S, Lewis LR, Nazareth LV, Okwuonu G, Santibanez J, Warren WC, Mardis ER, Weinstock GM, Wilson RK; Genome Institute at Washington University, Delehaunty K, Dooling D, Fronik C, Fulton L, Fulton B, Graves T, Minx P, Sodergren E, Birney E, Margulies EH, Herrero J, Green ED, Haussler D, Siepel A, Goldman N, Pollard KS, Pedersen JS, Lander ES, Kellis M.
Nature. 2011 Oct 12;478(7370):476-82.

Neural-specific elongation of 3′ UTRs during Drosophila development.
Hilgers V, Perry MW, Hendrix D, Stark A, Levine M, Haley B.
Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):15864-9.

A systematic analysis of Drosophila TUDOR domain-containing proteins identifies Vreteno and the Tdrd12 family as essential primary piRNA pathway factors.
Handler D, Olivieri D, Novatchkova M, Gruber FS, Meixner K, Mechtler K, Stark A, Sachidanandam R, Brennecke J.
EMBO J. 2011 Aug 23;30(19):3977-93.

High conservation of transcription factor binding and evidence for combinatorial regulation across six Drosophila species.
He Q, Bardet AF, Patton B, Purvis J, Johnston J, Paulson A, Gogol M, Stark A, Zeitlinger J.
Nat Genet. 2011 May;43(5):414-20.