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Jun Prof Mathias Munschauer

LncRNA and Infection Biology

The lab of Dr. Mathias Munschauer focuses on decoding the molecular mechanisms of long non-coding RNA by dissecting their biochemical interactions and molecular design principles. The group seeks to better understand the role of lncRNA in a host cell’s response to bacterial and viral infections with the ultimate goal of enhancing our ability to treat infectious diseases.

Our research and approach

RNA is a truly remarkable molecule with functions and activities far beyond that of an intermediate information carrier. The abundant class of long non-coding RNAs (lncRNAs) contains highly specialized RNA with structural or regulatory functions that range from assembling large protein complexes to localizing, sequestering, or allosterically modifying proteins and other interaction partners. Our genome contains thousands of lncRNAs, many of which are specifically regulated during bacterial or viral infections. However, their contribution to launching and sustaining an effective host response remains elusive. Our group combines a cutting-edge suite of technologies from the fields of biochemistry, genomics, molecular biology, and computational biology to decode how lncRNA work mechanistically and how they contribute to host defense mechanisms.

Team members

Jens Ade

Jens Ade

PhD Student

Sabina Ganskih

Sabina Ganskih

PhD Student

Yuanjie Wei

Yuanjie Wei

PhD Student

Simone Werner

Simone Werner

Technical Assistant

Research projects

To effectively combat invading pathogens, host cells need to be able to rapidly adjust their gene expression programs and mount an effective host response. In addition to messenger RNA (mRNA), thousands of so called long non-coding RNAs (lncRNAs) are actively transcribed and specifically regulated as a result of bacterial or viral infections. While lncRNA resembles their protein coding counterparts in length, splicing structure, and biochemical properties, they do not serve as templates for protein synthesis. Hence, their physiological functions and biochemical mechanisms are challenging to dissect and in many cases remain poorly understood. 

Recent breakthroughs in DNA sequencing technologies led to the realization that many lncRNAs are potent regulators of various gene expression programs, including the host response to pathogens. Knowledge of hundreds to thousands of pathogen-responsive lncRNAs can be considered a treasure trove for discovering novel mechanisms of gene regulation and host defense strategies. 

Our group aims to decipher the genetic code controlling lncRNA function by obtaining a quantitative understanding of their molecular interactions and decoding the sequence features or structural elements that mediate these interactions. We seek to elucidate the composition of lncRNA complexes and aim to identify biochemical interactions that enable lncRNA functions. In this context, we are particularly interested in broadly exploring our recent finding that lncRNAs can modulate proteins and control their ability to assemble higher-order ribonucleoprotein complexes. Our group is developing and applying cutting-edge technologies to characterize direct interactions of individual RNA species with proteins at high resolution and in a quantitative manner. Ultimately, we hope to utilize insights into the mechanisms of lncRNA function in order to improve our understanding and ability to treat infectious disease.
 

Publications

2020

Control of human hemoglobin switching by LIN28B-mediated regulation of BCL11A translation

Basak A, Munschauer M, Lareau CA, Montbleau KE, Ulirsch JC, Hartigan CR, Schenone M, Lian J, Wang Y, Huang Y, …, Lander ES, Sankaran VG (2020)

Nature Genetics 52 (2): 138-145

The lncRNA lincNMR regulates nucleotide metabolism via a YBX1 - RRM2 axis in cancer

Gandhi M, Groß M, Holler JM, Coggins SA, Patil N, Leupold JH, Munschauer M, Schenone M, Hartigan CR, Allgayer H, Kim B, Diederichs S (2020)

Nature Communications 11: 3214

The SARS-CoV-2 RNA-protein interactome in infected human cells

Schmidt N, Lareau CA, Keshishian H, Ganskih S, Schneider C, Hennig T, Melanson R, Werner S, Wei Y, Zimmer M, …, Bodem J, Munschauer M (2020)

Nature Microbiology 6 (3): 339-353

2019

Context-specific regulation of cell survival by a miRNA-controlled BIM rheostat

Labi V, Peng S, Klironomos F, Munschauer M, Kastelic N, Chakraborty T, Schoeler K, Derudder E, Martella M, Mastrobuoni G, …, Rajewsky N, Rajewsky K (2019)

Genes & Development 33 (23-24): 1673-1687

2018

Ribosome Levels Selectively Regulate Translation and Lineage Commitment in Human Hematopoiesis

Khajuria RK, Munschauer M, Ulirsch JC, Fiorini C, Ludwig LS, McFarland SK, Abdulhay NJ, Specht H, Keshishian H, Mani DR, …, Carr SA, Sankaran VG (2018)

Cell 173 (1): 90-103

The NORAD lncRNA assembles a topoisomerase complex critical for genome stability

Munschauer M, Nguyen CT, Sirokman K, Hartigan CR, Hogstrom L, Engreitz JM, Ulirsch JC, Fulco CP, Subramanian V, Chen J, …, Carr SA, Lander ES (2018)

Nature 561 (7721): 132-136

Nuclear lncRNA stabilization in the host response to bacterial infection

Munschauer M, Vogel J (2018)

The EMBO Journal 37 (13): 99875

New insights into the cellular temporal response to proteostatic stress

Rendleman J, Cheng Z, Maity S, Kastelic N, Munschauer M, Allgoewer K, Teo G, Zhang YB, Lei A, Parker B, …, Choi H, Vogel C (2018)

eLife 7: 39054

2017

Developmentally-faithful and effective human erythropoiesis in immunodeficient and Kit mutant mice

Fiorini C, Abdulhay NJ, McFarland SK, Munschauer M, Ulirsch JC, Chiarle R, Sankaran VG (2017)

American Journal of Hematology 92 (9): 513-

2016

Systematic mapping of functional enhancer-promoter connections with CRISPR interference

Fulco CP, Munschauer M, Anyoha R, Munson G, Grossman SR, Perez EM, Kane M, Cleary B, Lander ES, Engreitz JM (2016)

Science 354 (6313): 769-773

2015

Comprehensive Protein Interactome Analysis of a Key RNA Helicase: Detection of Novel Stress Granule Proteins

Bish R, Cuevas-Polo N, Cheng Z, Hambardzumyan D, Munschauer M, Landthaler M, Vogel C (2015)

Biomolecules 5 (3): 1441-66

2014

MOV10 Is a 5' to 3' RNA helicase contributing to UPF1 mRNA target degradation by translocation along 3' UTRs

Gregersen LH, Schueler M, Munschauer M, Mastrobuoni G, Chen W, Kempa S, Dieterich C, Landthaler M (2014)

Molecular Cell 54 (4): 573-85

Differential protein occupancy profiling of the mRNA transcriptome

Schueler M, Munschauer M, Gregersen LH, Finzel A, Loewer A, Chen W, Landthaler M, Dieterich C (2014)

Genome Biology 15 (1): 15

High-resolution profiling of protein occupancy on polyadenylated RNA transcripts

Munschauer M, Schueler M, Dieterich C, Landthaler M (2014)

Methods 65 (3): 302-9

2013

Circular RNAs are a large class of animal RNAs with regulatory potency

Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak SD, Gregersen LH, Munschauer M, …, Le Noble F, Rajewsky N (2013)

Nature 495 (7441): 333-8

Identification of LIN28B-bound mRNAs reveals features of target recognition and regulation

Graf R, Munschauer M, Mastrobuoni G, Mayr F, Heinemann U, Kempa S, Rajewsky N, Landthaler M (2013)

RNA Biology 10 (7): 1146-59

2012

The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts

Baltz AG, Munschauer M, Schwanhäusser B, Vasile A, Murakawa Y, Schueler M, Youngs N, Penfold-Brown D, Drew K, Milek M, …, Dieterich C, Landthaler M (2012)

Molecular Cell 46 (5): 674-90

FMRP targets distinct mRNA sequence elements to regulate protein expression

Ascano M, Mukherjee N, Bandaru P, Miller JB, Nusbaum JD, Corcoran DL, Langlois C, Munschauer M, Dewell S, Hafner M, …, Ohler U, Tuschl T (2012)

Nature 492 (7429): 382-6

2010

Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP

Hafner M, Landthaler M, Burger L, Khorshid M, Hausser J, Berninger P, Rothballer A, Ascano M, Jungkamp A, Munschauer M, …, Zavolan M, Tuschl T (2010)

Cell 141 (1): 129-41

PAR-CliP--a method to identify transcriptome-wide the binding sites of RNA binding proteins

Hafner M, Landthaler M, Burger L, Khorshid M, Hausser J, Berninger P, Rothballer A, Ascano M, Jungkamp A, Munschauer M, …, Zavolan M, Tuschl T (2010)

Journal of Visualized Experiments (41): 2034