Overview

The RNA Molecular Biology Laboratory (RMBL) 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 RMBL 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:

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

Core Research Facilities

Labs at the NIAMS are supported by the following state-of-the-art facilities and services:

Staff

Former Lab Members

Research Fellows

  • Daniel Benhalevy, Ph.D., 2016-2022; Assistant Professor (Tenure-Track), Tel Aviv University, Israel
  • Amir Manzourolajdad, 2019-2021; Visiting Assistant Professor, Colgate University

Postdoctoral Fellows

  • Aishe Angeletti Sarshad, Ph.D., 2014-2018; Assistant Professor (Tenure-Track), Gothenburg University, Sweden
  • Suman Ghosal, Ph.D., 2016-2017; Clinical Genomics Specialist, Guidehouse/NIAID
  • Tara Dutka, Ph.D., 2014-2016; Program Director, NIH

Predoctoral Fellows

  • Alexandra Balvey Gil, 2023;  Pre-doctoral Fellow, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain
  • Arwa Fallatah, M.Sc., 2017-2021; Postdoctoral Fellow, CCR/NCI

Postbaccalaureate Fellows

  • Emma Young, 2021 - 2023; Graduate Student, UCLA
  • Delaney Ahn, 2021-2022
  • Duncan Claypool, 2018-2020; M.D./Ph.D. student, University of Illinois in Chicago
  • Alexis Jacob, 2018-2020; Ph.D. student, Northwestern University
  • Nicole Johnson, 2017-2019; Research Program Coordinator, Johns Hopkins University School of Medicine
  • Ana I. Correa Muler, 2016-2018; Ph.D. student, Gothenburg University, Sweden
  • Hannah L. McFarland, 2015-2017; Senior Healthcare Consultant, Deloitte
  • Charles Danan, 2014-2016; M.D/Ph.D. student, University of Pennsylvania
  • Sudhir Manickavel, 2014-2015; Resident, University of Alabama Medical School

Image & Media Gallery

Scientific Publications

Selected Recent Publications

Matrin3 regulates mitotic spindle dynamics by controlling alternative splicing of CDC14B.

Muys BR, Shrestha RL, Anastasakis DG, Pongor L, Li XL, Grammatikakis I, Polash A, Chari R, Gorospe M, Harris CC, Aladjem MI, Basrai MA, Hafner M, Lal A
Cell Rep.
2023 Mar 28;
42(3).
doi: 10.1016/j.celrep.2023.112260
PMID: 36924503

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

Enhancement of LIN28B-induced hematopoietic reprogramming by IGF2BP3.

Wang S, Chim B, Su Y, Khil P, Wong M, Wang X, Foroushani A, Smith PT, Liu X, Li R, Ganesan S, Kanellopoulou C, Hafner M, Muljo SA
Genes Dev.
2019 Aug 1;
33(15-16).
doi: 10.1101/gad.325100.119
PMID: 31221665

DHX36 prevents the accumulation of translationally inactive mRNAs with G4-structures in untranslated regions.

Sauer M, Juranek SA, Marks J, De Magis A, Kazemier HG, Hilbig D, Benhalevy D, Wang X, Hafner M, Paeschke K
Nat Commun.
2019 Jun 3;
10(1).
doi: 10.1038/s41467-019-10432-5
PMID: 31160600

miR-450a Acts as a Tumor Suppressor in Ovarian Cancer by Regulating Energy Metabolism.

Muys BR, Sousa JF, Plaça JR, de Araújo LF, Sarshad AA, Anastasakis DG, Wang X, Li XL, de Molfetta GA, Ramão A, Lal A, Vidal DO, Hafner M, Silva WA
Cancer Res.
2019 Jul 1;
79(13).
doi: 10.1158/0008-5472.CAN-19-0490
PMID: 31101765

The splicing factor U2AF1 contributes to cancer progression through a noncanonical role in translation regulation.

Palangat M, Anastasakis DG, Fei DL, Lindblad KE, Bradley R, Hourigan CS, Hafner M, Larson DR
Genes Dev.
2019 May 1;
33(9-10).
doi: 10.1101/gad.319590.118
PMID: 30842218

Proximity-CLIP provides a snapshot of protein-occupied RNA elements in subcellular compartments.

Benhalevy D, Anastasakis DG, Hafner M
Nat Methods.
2018 Dec;
15(12).
doi: 10.1038/s41592-018-0220-y
PMID: 30478324

Argonaute-miRNA Complexes Silence Target mRNAs in the Nucleus of Mammalian Stem Cells.

Sarshad AA, Juan AH, Muler AIC, Anastasakis DG, Wang X, Genzor P, Feng X, Tsai PF, Sun HW, Haase AD, Sartorelli V, Hafner M
Mol Cell.
2018 Sep 20;
71(6).
doi: 10.1016/j.molcel.2018.07.020
PMID: 30146314

Human proteins that interact with RNA/DNA hybrids.

Wang IX, Grunseich C, Fox J, Burdick J, Zhu Z, Ravazian N, Hafner M, Cheung VG
Genome Res.
2018 Sep;
28(9).
doi: 10.1101/gr.237362.118
PMID: 30108179

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 Rep.
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

Key Publications

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 in subcellular compartments.

Benhalevy D, Anastasakis DG, Hafner M
Nat Methods.
2018 Dec;
15(12).
doi: 10.1038/s41592-018-0220-y
PMID: 30478324

Argonaute-miRNA Complexes Silence Target mRNAs in the Nucleus of Mammalian Stem Cells.

Sarshad AA, Juan AH, Muler AIC, Anastasakis DG, Wang X, Genzor P, Feng X, Tsai PF, Sun HW, Haase AD, Sartorelli V, Hafner M
Mol Cell.
2018 Sep 20;
71(6).
doi: 10.1016/j.molcel.2018.07.020
PMID: 30146314

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

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

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