PMID- 32927736
OWN - NLM
STAT- MEDLINE
DCOM- 20210302
LR  - 20210302
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 18
DP  - 2020 Sep 10
TI  - JMJD6 Regulates Splicing of Its Own Gene Resulting in Alternatively Spliced 
      Isoforms with Different Nuclear Targets.
LID - 10.3390/ijms21186618 [doi]
LID - 6618
AB  - Jumonji-domain-containing protein 6 (JMJD6) is a Fe(II) and 2-oxogluterate (2OG) 
      dependent oxygenase involved in gene regulation through post-translationally 
      modifying nuclear proteins. It is highly expressed in many cancer types and 
      linked to tumor progression and metastasis. Four alternatively-spliced jmjd6 
      transcripts were annotated. Here, we focus on the two most abundantly expressed 
      ones, which we call jmjd6-2 and jmjd6-Ex5. TCGA SpliceSeq data revealed a 
      significant decrease of jmjd6-Ex5 transcripts in patients and postmortem tissue 
      of several tumors. The two protein isoforms are distinguished by their C-terminal 
      sequences, which include a serine-rich region (polyS-domain) in JMJD6-2 that is 
      not present in JMJD6-Ex5. Immunoprecipitation followed by LC-MS/MS for JMJD6-Ex5 
      shows that different sets of proteins interact with JMJD6-2 and JMJD6-Ex5 with 
      only a few overlaps. In particular, we found TFIIF-associating CTD phosphatase 
      (FCP1), proteins of the survival of motor neurons (SMN) complex, heterogeneous 
      nuclear ribonucleoproteins (hnRNPs) and upstream binding factor (UBF) to interact 
      with JMJD6-Ex5. Like JMJD6-2, both UBF and FCP1 comprise a polyS-domain. The 
      polyS domain of JMJD6-2 might block the interaction with polyS-domains of other 
      proteins. In contrast, JMJD6-2 interacts with many SR-like proteins with 
      arginine/serine-rich (RS)-domains, including several splicing factors. In an 
      HIV-based splicing reporter assay, co-expression of JMJD6-2 inhibited exon 
      inclusion, whereas JMJD6-Ex5 did not have any effect. Furthermore, the silencing 
      of jmjd6 by siRNAs favored jmjd6-Ex5 transcripts, suggesting that JMJD6 controls 
      splicing of its own pre-mRNA. The distinct molecular properties of JMJD6-2 and 
      JMJD6-Ex5 open a lead into the functional implications of the variations of their 
      relative abundance in tumors.
FAU - Raguz, Nikoleta
AU  - Raguz N
AD  - Department of Biology II, Ludwig Maximilians University, Munich, Grosshaderner 
      Strasse 2, 82152 Planegg-Martinsried, Germany.
AD  - Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum 
      Munchen-German Research Center for Environmental Health, Ingolstadter Landstrasse 
      1, 85764 Neuherberg, Germany.
FAU - Heim, Astrid
AU  - Heim A
AD  - Department of Biology II, Ludwig Maximilians University, Munich, Grosshaderner 
      Strasse 2, 82152 Planegg-Martinsried, Germany.
FAU - Engal, Eden
AU  - Engal E
AD  - Department of Biochemistry and Molecular Biology, Institute for Medical Research 
      Israel Canada, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 
      91120, Israel.
FAU - Wesche, Juste
AU  - Wesche J
AD  - Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum 
      Munchen-German Research Center for Environmental Health, Ingolstadter Landstrasse 
      1, 85764 Neuherberg, Germany.
FAU - Merl-Pham, Juliane
AU  - Merl-Pham J
AD  - Research Unit Protein Science, Helmholtz Zentrum Munchen-German Research Center 
      for Environmental Health, Ingolstadter Landstrasse 1, 85764 Neuherberg, Germany.
FAU - Hauck, Stefanie M
AU  - Hauck SM
AD  - Research Unit Protein Science, Helmholtz Zentrum Munchen-German Research Center 
      for Environmental Health, Ingolstadter Landstrasse 1, 85764 Neuherberg, Germany.
FAU - Erkelenz, Steffen
AU  - Erkelenz S
AD  - Institute for Genetics and Cologne Excellence Cluster on Cellular Stress 
      Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 
      Cologne, Germany.
FAU - Schaal, Heiner
AU  - Schaal H
AUID- ORCID: 0000-0002-1636-4365
AD  - Institute of Virology, Medical Faculty, Heinrich Heine University Duesseldorf, 
      40225 Duesseldorf, Germany.
FAU - Bensaude, Olivier
AU  - Bensaude O
AD  - Institute de Biologie de l'Ecole Normale Superiuere (IBENS), Ecole Normale 
      Superieure, CNRS, INSERM, PSL Research University, 5005 Paris, France.
FAU - Wolf, Alexander
AU  - Wolf A
AD  - Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum 
      Munchen-German Research Center for Environmental Health, Ingolstadter Landstrasse 
      1, 85764 Neuherberg, Germany.
FAU - Salton, Maayan
AU  - Salton M
AUID- ORCID: 0000-0001-8812-5577
AD  - Department of Biochemistry and Molecular Biology, Institute for Medical Research 
      Israel Canada, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 
      91120, Israel.
FAU - Bottger, Angelika
AU  - Bottger A
AD  - Department of Biology II, Ludwig Maximilians University, Munich, Grosshaderner 
      Strasse 2, 82152 Planegg-Martinsried, Germany.
LA  - eng
GR  - I-1436-417.13/2017/German-Israeli Foundation for Scientific Research and 
      Development/
PT  - Comparative Study
PT  - Journal Article
DEP - 20200910
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Protein Isoforms)
RN  - EC 1.14.11.- (JMJD6 protein, human)
RN  - EC 1.14.11.- (Jumonji Domain-Containing Histone Demethylases)
SB  - IM
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Humans
MH  - Jumonji Domain-Containing Histone Demethylases/genetics/*metabolism
MH  - Neoplasms/metabolism
MH  - Protein Domains
MH  - Protein Isoforms/chemistry/metabolism
MH  - *RNA Splicing
PMC - PMC7555845
OTO - NOTNLM
OT  - hydroxylation
OT  - polyS domain
OT  - splicing
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2020/09/16 06:00
MHDA- 2021/03/03 06:00
PMCR- 2020/09/01
CRDT- 2020/09/15 01:03
PHST- 2020/08/14 00:00 [received]
PHST- 2020/09/03 00:00 [revised]
PHST- 2020/09/08 00:00 [accepted]
PHST- 2020/09/15 01:03 [entrez]
PHST- 2020/09/16 06:00 [pubmed]
PHST- 2021/03/03 06:00 [medline]
PHST- 2020/09/01 00:00 [pmc-release]
AID - ijms21186618 [pii]
AID - ijms-21-06618 [pii]
AID - 10.3390/ijms21186618 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Sep 10;21(18):6618. doi: 10.3390/ijms21186618.