Summary

Markus Hafner, Ph.D., joined the Laboratory of Muscle Stem Cells and Gene Regulation as an Investigator in 2014. Before his appointment at the NIAMS, he was a postdoctoral fellow in the Laboratory of Dr. Thomas Tuschl at the Rockefeller University in New York. There he worked on mechanisms of gene silencing by small RNAs, and developed methods to characterize post-transcriptional gene regulation by RNA binding proteins.

Before coming to the United States, Dr. Hafner lived in Germany, Mexico, China, Greece, and Honduras. He obtained an M.Sc. in chemistry in 2002 and a Ph.D. in biochemistry in 2007 from the University of Bonn, Germany. His graduate work under Dr. Michael Famulok focused on the use of RNA aptamers to select small molecule inhibitors for cytohesins, a family of guanosine exchange factors, which revealed their role in the insulin signaling pathway.

In his laboratory at NIAMS, Dr. Hafner will focus on dissecting the composition of ribonucleoproteins (RNPs) involved in cellular RNA transport and control of RNA stability. This is a prerequisite for understanding the consequences of dysregulation and/or mutation of RNA-binding proteins (RBPs), and/or their target RNA-binding sites in disease.

Research Statement

A rough categorization of interconnected posttranscriptional gene regulatory processes based on cellular compartmentalization.
Figure 1

The RNA Molecular Biology Group (RMBG) studies the impact of RNA binding proteins (RBPs) on posttranscriptional gene regulation (PTGR). PTGR summarizes various processes acting upon coding and non-coding RNA and includes RNA maturation, ribonucleoprotein (RNP) assembly, transport, translation, and turnover (Figure 1).

The recent introduction of large-scale quantitative methods, such as next-generation sequencing (NGS) and modern mass spectrometry (MS), allows for the first time determination of the functional impact of RBPs on a system-wide level and has sparked a renewed interest in the systematic characterization of PTGR processes.

Members of the RMBG focus on elucidating the function and molecular mechanisms of RNA binding proteins involved in RNA transport, RNA stability and turnover, and RNA translation. Broadly, we are pursuing four interdependent projects:

  • Investigate the role of predicted AU-rich element binding proteins in determining mRNA turnover. 
  • Identify and characterize the interaction network of mRNA binding transport and shuttling proteins and their RNA targets at a sequence and functional level. 
  • Investigate the impact of select RBPs on translation initiation and elongation. 
  • Integrate the results from our systems-level determination of cis-acting elements into high-resolution maps of posttranscriptional regulatory events. 

Scientific Publications

A non-radioactive, improved PAR-CLIP and small RNA cDNA library preparation protocol.

Anastasakis DG, Jacob A, Konstantinidou P, Meguro K, Claypool D, Cekan P, Haase AD, Hafner M
Nucleic Acids Res.
2021 May 7;
49(8).
doi: 10.1093/nar/gkab011
PMID: 33503264

Posttranscriptional regulation of human endogenous retroviruses by RNA-binding motif protein 4, RBM4.

Foroushani AK, Chim B, Wong M, Rastegar A, Smith PT, Wang S, Barbian K, Martens C, Hafner M, Muljo SA
Proc Natl Acad Sci U S A.
2020 Oct 20;
117(42).
doi: 10.1073/pnas.2005237117
PMID: 33020268

Proximity-CLIP Provides a Snapshot of Protein-Occupied RNA Elements at Subcellular Resolution and Transcriptome-Wide Scale.

Benhalevy D, Hafner M
Methods Mol Biol.
2020;
2166().
doi: 10.1007/978-1-0716-0712-1_17
PMID: 32710416

PAR-CLIP and streamlined small RNA cDNA library preparation protocol for the identification of RNA binding protein target sites.

Benhalevy D, McFarland HL, Sarshad AA, Hafner M
Methods.
2017 Apr 15;
118-119().
doi: 10.1016/j.ymeth.2016.11.009
PMID: 27871973

PAR-CLIP: A Method for Transcriptome-Wide Identification of RNA Binding Protein Interaction Sites.

Danan C, Manickavel S, Hafner M
Methods Mol Biol.
2016;
1358().
doi: 10.1007/978-1-4939-3067-8_10
PMID: 26463383

PAR-CLIP analysis uncovers AUF1 impact on target RNA fate and genome integrity.

Yoon JH, De S, Srikantan S, Abdelmohsen K, Grammatikakis I, Kim J, Kim KM, Noh JH, White EJ, Martindale JL, Yang X, Kang MJ, Wood WH 3rd, Noren Hooten N, Evans MK, Becker KG, Tripathi V, Prasanth KV, Wilson GM, Tuschl T, Ingolia NT, Hafner M, Gorospe M
Nat Commun.
2014 Nov 4;
5().
doi: 10.1038/ncomms6248
PMID: 25366541

A census of human RNA-binding proteins.

Gerstberger S, Hafner M, Tuschl T
Nat Rev Genet.
2014 Dec;
15(12).
doi: 10.1038/nrg3813
PMID: 25365966

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 Jr, Jungkamp AC, Munschauer M, Ulrich A, Wardle GS, Dewell S, Zavolan M, Tuschl T
Cell.
2010 Apr 2;
141(1).
doi: 10.1016/j.cell.2010.03.009
PMID: 20371350

Inhibition of cytohesins by SecinH3 leads to hepatic insulin resistance.

Hafner M, Schmitz A, Grüne I, Srivatsan SG, Paul B, Kolanus W, Quast T, Kremmer E, Bauer I, Famulok M
Nature.
2006 Dec 14;
444(7121).

Education

University of Bonn, Germany
Diploma in Chemistry (M.Sc. equivalent), 1997

University of Bonn, Germany
Ph.D., Biochemistry, 2007

Experience

Senior Investigator
NIAMS/NIH, 2019–present

Tenure-Track Investigator
NIAMS/NIH, 2014–2019

Postdoctoral Fellowship
Rockefeller University, New York, 2007–2014

Graduate Work
University of Bonn, Germany, 2002–2007

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