Research



Gene expression is the fundamental process that uses the genomic information in order to synthesize gene products. We focus on understanding the general mechanisms and processes that regulate gene expression and thereby ensure faithful protein production. Specifically, we are interested how ribonucleoprotein (RNP) complexes influence various stages of the messenger RNA (mRNA) lifecycle. More detailed information about ongoing research projects in the lab can be found below.


Exon junction complex

From the moment when a mRNA is first transcribed by the RNA polymerase, RNA-binding proteins associate with this transcript and influence its fate. One protein complex in particular, called the exon junction complex (EJC), is deposited on the mRNA during splicing. The EJC remains bound on the mRNA until it is displaced in the cytoplasm by ribosomes. Until then, the EJC regulates alternative splicing, enhances nuclear mRNA export, stimulates translation and ultimately, is involved in quality control (see nonsense-mediated mRNA decay).
EJC research
We currently investiage how the EJC is assembled in the first place, which factors are required for this, and how the EJC exerts its many functions on gene expression.

Key publications:

Gehring NH, Wahle E, Fischer U.
Deciphering the mRNP Code: RNA-Bound Determinants of Post-Transcriptional Gene Regulation
Trends Biochem Sci. 2017 Mar 3. pii: S0968-0004(17)30043-9. doi: 10.1016/j.tibs.2017.02.004.
PubMed


Boehm V, Gehring NH.
Exon Junction Complexes: Supervising the Gene Expression Assembly Line.
Trends Genet. 2016 Nov;32(11):724-735. doi: 10.1016/j.tig.2016.09.003. Review.
PubMed


Steckelberg AL, Altmueller J, Dieterich C, Gehring NH.
CWC22-dependent pre-mRNA splicing and eIF4A3 binding enables global deposition of exon junction complexes.
Nucleic Acids Res. 2015 May 19;43(9):4687-700. doi: 10.1093/nar/gkv320.
PubMed


Steckelberg AL, Gehring NH.
Studying the composition of mRNPs in vitro using splicing-competent cell extracts.
Methods. 2014 Feb;65(3):342-9. doi: 10.1016/j.ymeth.2013.08.033.
PubMed

Nonsense-mediated mRNA decay

To maintain the correct translation of proteins in the cell, quality control mechanisms constantly monitor each step of gene expression. One of these mechanisms is the nonsense-mediated mRNA decay pathway, or short NMD. If due to mutations or other reasons, such as mistakes during pre-mRNA processing, a transcript contains a premature translation termination codon (PTC), this mRNA is detected by NMD and consequently degraded. Thereby, NMD generally protects the cell by preventing the translation of truncated proteins.
NMD pathway
Nevertheless, if the PTC-containing mRNAs in principle encode for partially functional proteins, as it is the case in certain diseases, the clinical phenotype could be alleviated by blocking NMD specifically. To better understand, how NMD is activated, how PTC-containing mRNAs are distinguished from normal ones, and how the transcripts are degraded in the end, we use molecular-biological and biochemical experimental approaches in cultured human cells.

Key publications:

Ottens F, Boehm V, Sibley CR, Ule J, Gehring NH.
Transcript-specific characteristics determine the contribution of endo- and exonucleolytic decay pathways during the degradation of nonsense-mediated decay substrates.
RNA 2017 May 1. pii: rna.059659.116 doi: 10.1261/rna.059659.116
PubMed


Boehm V, Gerbracht JV, Marx MC, Gehring NH.
Interrogating the degradation pathways of unstable mRNAs with XRN1-resistant sequences.
Nat Commun. 2016 Dec 5;7:13691. doi: 10.1038/ncomms13691.
PubMed


Fatscher T, Boehm V, Gehring NH.
Mechanism, factors, and physiological role of nonsense-mediated mRNA decay.
Cell Mol Life Sci. 2015 Dec;72(23):4523-44. doi: 10.1007/s00018-015-2017-9. Review.
PubMed


Boehm V, Haberman N, Ottens F, Ule J, Gehring NH.
3' UTR length and messenger ribonucleoprotein composition determine endocleavage efficiencies at termination codons.
Cell Rep. 2014 Oct 23;9(2):555-68. doi: 10.1016/j.celrep.2014.09.012.
PubMed


Fatscher T, Boehm V, Weiche B, Gehring NH.
The interaction of cytoplasmic poly(A)-binding protein with eukaryotic initiation factor 4G suppresses nonsense-mediated mRNA decay.
RNA. 2014 Oct;20(10):1579-92. doi: 10.1261/rna.044933.114.
PubMed

Other mRNA/mRNP research projects

Before an mRNA is translated in the cytoplasm, it has to be processed in the nucleus and transported to the cytoplasm. The export of mature mRNAs is tightly linked to nuclear pre-mRNA processing to ensure that only correctly processed transcripts are translated. The recruitment of the general mRNA export receptor NXF1/NXT1 to spliced mRNA involves different adaptor proteins. Some of these adaptor proteins (e.g. ALYREF) interact with the exon junction complex, which therefore provides a link between pre-mRNA splicing and export.

Key publications:

Gromadzka AM, Steckelberg AL, Singh KK, Hofmann K, Gehring NH.
A short conserved motif in ALYREF directs cap- and EJC-dependent assembly of export complexes on spliced mRNAs.
Nucleic Acids Res. 2016 Mar 18;44(5):2348-61. doi: 10.1093/nar/gkw009.
PubMed


People




Group Leader

Niels H. Gehring
Email
Researchgate

Technician

Juliane Hancke
Email

Post-Doc

Volker Böhm
Email
Researchgate

PhD Student

Jennifer Gerbracht
Email
Researchgate


Simona Ciriello

Tobias Fatscher

Agnieszka Gromadzka

Marie Charlotte Marx

Franziska Ottens

Kusum Singh

Anna-Lena Steckelberg

Heidi Thelen

Benjamin Weiche


Publications




  1. Gerbracht JV, Boehm V, Gehring NH.
    Plasmid transfection influences the readout of nonsense-mediated mRNA decay reporter assays in human cells.
    Sci Rep. 2017 Sep 6;7(1):10616. doi: 10.1038/s41598-017-10847-4.
    PubMed
  2. Ottens F, Boehm V, Sibley CR, Ule J, Gehring NH.
    Transcript-specific characteristics determine the contribution of endo- and exonucleolytic decay pathways during the degradation of nonsense-mediated decay substrates.
    RNA 2017 May 1. pii: rna.059659.116 doi: 10.1261/rna.059659.116
    PubMed
  3. Gehring NH, Wahle E, Fischer U.
    Deciphering the mRNP Code: RNA-Bound Determinants of Post-Transcriptional Gene Regulation
    Trends Biochem Sci. 2017 Mar 3. pii: S0968-0004(17)30043-9. doi: 10.1016/j.tibs.2017.02.004.
    PubMed

  1. Boehm V, Gerbracht JV, Marx MC, Gehring NH.
    Interrogating the degradation pathways of unstable mRNAs with XRN1-resistant sequences.
    Nat Commun. 2016 Dec 5;7:13691. doi: 10.1038/ncomms13691.
    PubMed
  2. Fatscher T, Gehring NH.
    Harnessing short poly(A)-binding protein-interacting peptides for the suppression of nonsense-mediated mRNA decay.
    Sci Rep. 2016 Nov 22;6:37311. doi: 10.1038/srep37311.
    PubMed
  3. Boehm V, Gehring NH.
    Exon Junction Complexes: Supervising the Gene Expression Assembly Line.
    Trends Genet. 2016 Nov;32(11):724-735. doi: 10.1016/j.tig.2016.09.003. Review.
    PubMed
  4. Ottens F, Gehring NH.
    Physiological and pathophysiological role of nonsense-mediated mRNA decay.
    Pflugers Arch. 2016 Jun;468(6):1013-28. doi: 10.1007/s00424-016-1826-5. Review.
    PubMed
  5. Gromadzka AM, Steckelberg AL, Singh KK, Hofmann K, Gehring NH.
    A short conserved motif in ALYREF directs cap- and EJC-dependent assembly of export complexes on spliced mRNAs.
    Nucleic Acids Res. 2016 Mar 18;44(5):2348-61. doi: 10.1093/nar/gkw009.
    PubMed

  1. Ajamian L, Abel K, Rao S, Vyboh K, García-de-Gracia F, Soto-Rifo R, Kulozik AE, Gehring NH, Mouland AJ.
    HIV-1 Recruits UPF1 but Excludes UPF2 to Promote Nucleocytoplasmic Export of the Genomic RNA.
    Biomolecules. 2015 Oct 20;5(4):2808-39. doi: 10.3390/biom5042808.
    PubMed
  2. Fatscher T, Boehm V, Gehring NH.
    Mechanism, factors, and physiological role of nonsense-mediated mRNA decay.
    Cell Mol Life Sci. 2015 Dec;72(23):4523-44. doi: 10.1007/s00018-015-2017-9. Review.
    PubMed
  3. Linder B, Fischer U, Gehring NH.
    mRNA metabolism and neuronal disease.
    FEBS Lett. 2015 Jun 22;589(14):1598-606. doi: 10.1016/j.febslet.2015.04.052. Review.
    PubMed
  4. Steckelberg AL, Altmueller J, Dieterich C, Gehring NH.
    CWC22-dependent pre-mRNA splicing and eIF4A3 binding enables global deposition of exon junction complexes.
    Nucleic Acids Res. 2015 May 19;43(9):4687-700. doi: 10.1093/nar/gkv320.
    PubMed
  5. Stockklausner C, Klotter AC, Dickemann N, Kuhlee IN, Duffert CM, Kerber C, Gehring NH, Kulozik AE.
    The thrombopoietin receptor P106L mutation functionally separates receptor signaling activity from thrombopoietin homeostasis.
    Blood. 2015 Feb 12;125(7):1159-69. doi: 10.1182/blood-2014-07-587170.
    PubMed

  1. Boehm V, Haberman N, Ottens F, Ule J, Gehring NH.
    3' UTR length and messenger ribonucleoprotein composition determine endocleavage efficiencies at termination codons.
    Cell Rep. 2014 Oct 23;9(2):555-68. doi: 10.1016/j.celrep.2014.09.012.
    PubMed
  2. Fatscher T, Boehm V, Weiche B, Gehring NH.
    The interaction of cytoplasmic poly(A)-binding protein with eukaryotic initiation factor 4G suppresses nonsense-mediated mRNA decay.
    RNA. 2014 Oct;20(10):1579-92. doi: 10.1261/rna.044933.114.
    PubMed
  3. Burgute BD, Peche VS, Steckelberg AL, Glöckner G, Gaßen B, Gehring NH, Noegel AA.
    NKAP is a novel RS-related protein that interacts with RNA and RNA binding proteins.
    Nucleic Acids Res. 2014 Mar;42(5):3177-93. doi: 10.1093/nar/gkt1311.
    PubMed
  4. Clerici M, Deniaud A, Boehm V, Gehring NH, Schaffitzel C, Cusack S.
    Structural and functional analysis of the three MIF4G domains of nonsense-mediated decay factor UPF2.
    Nucleic Acids Res. 2014 Feb;42(4):2673-86. doi: 10.1093/nar/gkt1197.
    PubMed
  5. Steckelberg AL, Gehring NH.
    Studying the composition of mRNPs in vitro using splicing-competent cell extracts.
    Methods. 2014 Feb;65(3):342-9. doi: 10.1016/j.ymeth.2013.08.033.
    PubMed

For the full list of publications by the Gehring Lab, follow this link.


Opportunities for Master and Bachelor Theses, Lab Modules

Please send inquiries for Bachelor and Master theses or laboratory modules including a short CV to Niels Gehring.