Prof Mathias Munschauer

LncRNA and Infection Biology

Our research and approach

The research group led by Mathias Munschauer investigates host and pathogen RNA-protein interactions in an infection context. They work towards obtaining a mechanistic understanding of RNA functions during infection, which will ultimately aid the development of host-directed therapeutics.

Viruses are a burden to human health. Identifying host cell factors that bind and regulate viral RNA during infection processes is important for understanding how viruses can take over a host cell, subvert host processes and escape innate immune defense mechanisms. Insights into the underlying molecular interactions and mechanisms contribute towards the development of novel RNA-based therapies.

Mathias Munschauer´s group is charting a map of functionally important RNA-protein interactions for specific RNA types, ranging from host or pathogen encoded long non-coding RNAs (lncRNAs) to viral RNA genomes. Their work combines a cutting-edge suite of technologies from the fields of biochemistry, genomics, molecular biology and computational biology.

They investigate RNA molecules by creating a snapshot of their protein interactions using RNA antisense purification and mass spectrometry (RAP-MS). Interactions are then functionally dissected using RNA-seq, Ribo-seq and CLIP-seq technologies. The group´s overarching goal is to create a map of functionally important RNA-protein interactions during infection processes to guide the development of novel host-directed therapeutics.

Team members

Group Leader

Postdoc

Postdoc

PhD Student

PhD Student

PhD Student

Technical Assistant

Research projects

Graphical Abstract

The research foci of the Munschauer lab
Graphical abstract © Helmholtz Institute Würzburg / Sandy Westermann

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.

A human factor

How SARS-CoV-2 initiates its replication process during infection is not yet fully understood. Researchers from the Munschauer lab have shown in the journal Cell that it is the human protein SND1 which works together with the viral protein NSP9 to stimulate the virus’s genetic replication program in infected cells.

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Publications

2024

Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts

Trifault B, Mamontova V, Cossa G, Ganskih S, Wei Y, Hofstetter J, Bhandare P, Baluapuri A, Nieto B, Solvie D, …, Munschauer M, Burger K (2024)

Nucleic Acids Research (Online ahead of print)

SHIFTR enables the unbiased identification of proteins bound to specific RNA regions in live cells

Aydin J, Gabel A, Zielinski S, Ganskih S, Schmidt N, Hartigan CR, Schenone M, Carr SA, Munschauer M (2024)

Nucleic Acids Research 52 (5): e26

2023

SND1 binds SARS-CoV-2 negative-sense RNA and promotes viral RNA synthesis through NSP9

Schmidt N, Ganskih S, Wei Y, Gabel A, Zielinski S, Keshishian H, Lareau CA, Zimmermann L, Makroczyova J, Pearce C, …, Erhard F, Munschauer M (2023)

Cell 186 (22): 4834-4850.e23

An RNA modification enzyme directly senses reactive oxygen species for translational regulation in Enterococcus faecalis

Lee WL, Sinha A, Lam LN, Loo HL, Liang J, Ho P, Cui L, Chan CSC, Begley T, Kline KA, Dedon P (2023)

Nature Communications 14 (1): 4093

Lab-scale siRNA and mRNA LNP manufacturing by various microfluidic mixing techniques – an evaluation of particle properties and efficiency

Jürgens DC, Deßloch L, Porras-Gonzalez D, Winkeljann J, Zielinski S, Munschauer M, Hörner AL, Burgstaller G, Winkeljann B, Merkel OM (2023)

OpenNano 12 (1): 100161

2022

Congenital anemia reveals distinct targeting mechanisms for master transcription factor GATA1

Ludwig LS, Lareau CA, Bao EL, Liu N, Utsugisawa T, Tseng AM, Myers SA, Verboon JM, Ulirsch JC, Luo W, …, Kanno H, Sankaran VG (2022)

Blood 139 (16): 2534-2546

Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection

Pekayvaz K, Leunig A, Kaiser R, Joppich M, Brambs S, Janjic A, Popp O, Nixdorf D, Fumagalli V, Schmidt N, …, Stark K, Nicolai L (2022)

Nature Communications 13 (1): 1018

2021

BRD9 is a druggable component of interferon-stimulated gene expression and antiviral activity

Börold J, Eletto D, Busnadiego I, Mair NK, Moritz E, Schiefer S, Schmidt N, Petric PP, Wong WW, Schwemmle M, Hale BG (2021)

EMBO reports 22 (10): e52823

Atlas der SARS-CoV-2-RNA-Protein-Interaktionen in infizierten Zellen

Schmidt N, Munschauer M (2021)

BIOspektrum 27 (4): 376-379

The Zinc Finger Antiviral Protein ZAP Restricts Human Cytomegalovirus and Selectively Binds and Destabilizes Viral UL4/UL5 Transcripts

Gonzalez-Perez AC, Stempel M, Wyler E, Urban C, Piras A, Hennig T, Ganskih S, Wei Y, Heim A, Landthaler M, …, Erhard F, Brinkmann MM (2021)

mBio 12 (3): e02683-20

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.e19

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): e99875

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: e39054

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): E513-E519

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): R15

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): pii: 2034