Overview

Principal Investigator

Markus Hafner, Ph.D.

Dr. Markus Hafner leads a team of scientists studying the impact of RNA binding proteins (RBPs) on posttranscriptional gene regulation (PTGR). Dr. Hafner’s research focuses on ribonucleoproteins (RNPs) involved in RNA transport and stability.

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

Scientific Publications

 

 

Aberrant tRNA processing causes an autoinflammatory syndrome responsive to TNF inhibitors.

Giannelou A, Wang H, Zhou Q, Park YH, Abu-Asab MS, Ylaya K, Stone DL, Sediva A, Sleiman R, Sramkova L, Bhatla D, Serti E, Tsai WL, Yang D, Bishop K, Carrington B, Pei W, Deuitch N, Brooks S, Edwan JH, Joshi S, Prader S, Kaiser D, Owen WC, Sonbul AA, Zhang Y, Niemela JE, Burgess SM, Boehm M, Rehermann B, Chae J, Quezado MM, Ombrello AK, Buckley RH, Grom AA, Remmers EF, Pachlopnik JM, Su HC, Gutierrez-Cruz G, Hewitt SM, Sood R, Risma K, Calvo KR, Rosenzweig SD, Gadina M, Hafner M, Sun HW, Kastner DL, Aksentijevich I
Annals of the rheumatic diseases.
2018 Apr;
77(4).
doi: 10.1136/annrheumdis-2017-212401
PMID: 29358286

Many si/shRNAs can kill cancer cells by targeting multiple survival genes through an off-target mechanism.

Putzbach W, Gao QQ, Patel M, van Dongen S, Haluck-Kangas A, Sarshad AA, Bartom ET, Kim KA, Scholtens DM, Hafner M, Zhao JC, Murmann AE, Peter ME
eLife.
2017 Oct 24;
6().
pii: e29702. doi: 10.7554/eLife.29702
PMID: 29063830

LARP4 mRNA codon-tRNA match contributes to LARP4 activity for ribosomal protein mRNA poly(A) tail length protection.

Mattijssen S, Arimbasseri AG, Iben JR, Gaidamakov S, Lee J, Hafner M, Maraia RJ
eLife.
2017 Sep 12;
6().
pii: e28889. doi: 10.7554/eLife.28889
PMID: 28895529

Characterizing Expression and Processing of Precursor and Mature Human tRNAs by Hydro-tRNAseq and PAR-CLIP.

Gogakos T, Brown M, Garzia A, Meyer C, Hafner M, Tuschl T
Cell reports.
2017 Aug 8;
20(6).
doi: 10.1016/j.celrep.2017.07.029
PMID: 28793268

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 (San Diego, Calif.).
2017 Apr 15;
118-119().
doi: 10.1016/j.ymeth.2016.11.009
PMID: 27871973

The Human CCHC-type Zinc Finger Nucleic Acid-Binding Protein Binds G-Rich Elements in Target mRNA Coding Sequences and Promotes Translation.

Benhalevy D, Gupta SK, Danan CH, Ghosal S, Sun HW, Kazemier HG, Paeschke K, Hafner M, Juranek SA
Cell reports.
2017 Mar 21;
18(12).
doi: 10.1016/j.celrep.2017.02.080
PMID: 28329689

DND1 maintains germline stem cells via recruitment of the CCR4-NOT complex to target mRNAs.

Yamaji M, Jishage M, Meyer C, Suryawanshi H, Der E, Yamaji M, Garzia A, Morozov P, Manickavel S, McFarland HL, Roeder RG, Hafner M, Tuschl T
Nature.
2017 Mar 23;
543(7646).
doi: 10.1038/nature21690
PMID: 28297718

Evolving specificity of tRNA 3-methyl-cytidine-32 (m3C32) modification: a subset of tRNAsSer requires N6-isopentenylation of A37.

Arimbasseri AG, Iben J, Wei FY, Rijal K, Tomizawa K, Hafner M, Maraia RJ
RNA (New York, N.Y.).
2016 Sep;
22(9).
doi: 10.1261/rna.056259.116
PMID: 27354703

Post-transcriptional Control of Tumor Cell Autonomous Metastatic Potential by CCR4-NOT Deadenylase CNOT7.

Faraji F, Hu Y, Yang HH, Lee MP, Winkler GS, Hafner M, Hunter KW
PLoS genetics.
2016 Jan;
12(1).
doi: 10.1371/journal.pgen.1005820
PMID: 26807845

Biochemical isolation of Argonaute protein complexes by Ago-APP.

Hauptmann J, Schraivogel D, Bruckmann A, Manickavel S, Jakob L, Eichner N, Pfaff J, Urban M, Sprunck S, Hafner M, Tuschl T, Deutzmann R, Meister G
Proceedings of the National Academy of Sciences of the United States of America.
2015 Sep 22;
112(38).
doi: 10.1073/pnas.1506116112
PMID: 26351695

Latest News

Research Brief | May 10, 2017

Germ Cell Formation in Mice Relies on RNA Clearance Mechanism

All of our cells, be they skin, muscle or bone, contain the same genetic material. Yet these cells appear different and have unique functions. Decades of research have revealed that the distinctions arise during development as a result of differential gene expression. Now, new work has revealed clues about how this process occurs.
Letter from the Director | February 25, 2016

Building Bridges to Enhance Patient Care: The NIAMS Intramural Research Program

The NIAMS Intramural Research Program (IRP), and the entire intramural program at NIH, offer unique resources in the biomedical research enterprise. The long-term, high-risk, high-reward focus of the IRP allows researchers to stretch the boundaries of innovation. They are able to build bridges across the traditional silos that tend to separate organizations, patients and scientists, and research results and clinical practice. These collaborations make an enormous difference for all Americans.
Spotlight on Research | September 15, 2015

NIAMS Interns Share Their 2015 Summer Experiences

Our 2015 summer interns received career mentoring from NIAMS researchers, attended lectures and symposia, engaged in basic and clinical research, and gained notable experience that will help them pursue their career goals. It is our pleasure to share with you their summer experiences.
Last Updated: May 2020