Universität zu Köln

Raguz, Nikoleta, Heim, Astrid, Engal, Eden, Wesche, Juste, Merl-Pham, Juliane ORCID: 0000-0002-3422-4083, Hauck, Stefanie M., Erkelenz, Steffen ORCID: 0000-0003-4763-1240, Schaal, Heiner ORCID: 0000-0002-1636-4365, Bensaude, Olivier, Wolf, Alexander, Salton, Maayan ORCID: 0000-0001-8812-5577 and Boettger, Angelika (2020). JMJD6 Regulates Splicing of Its Own Gene Resulting in Alternatively Spliced Isoforms with Different Nuclear Targets. Int. J. Mol. Sci., 21 (18). BASEL: MDPI. ISSN 1422-0067

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Abstract

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-splicedjmjd6transcripts were annotated. Here, we focus on the two most abundantly expressed ones, which we calljmjd6-2andjmjd6-Ex5.TCGA SpliceSeqdata revealed a significant decrease ofjmjd6-Ex5transcripts 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 ofjmjd6by siRNAs favoredjmjd6-Ex5transcripts, 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Raguz, Nikoleta UNSPECIFIED UNSPECIFIED UNSPECIFIED Heim, Astrid UNSPECIFIED UNSPECIFIED UNSPECIFIED Engal, Eden UNSPECIFIED UNSPECIFIED UNSPECIFIED Wesche, Juste UNSPECIFIED UNSPECIFIED UNSPECIFIED Merl-Pham, Juliane UNSPECIFIED orcid.org/0000-0002-3422-4083 UNSPECIFIED Hauck, Stefanie M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Erkelenz, Steffen UNSPECIFIED orcid.org/0000-0003-4763-1240 UNSPECIFIED Schaal, Heiner UNSPECIFIED orcid.org/0000-0002-1636-4365 UNSPECIFIED Bensaude, Olivier UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Salton, Maayan UNSPECIFIED orcid.org/0000-0001-8812-5577 UNSPECIFIED Boettger, Angelika UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-320353
DOI:	10.3390/ijms21186618
Journal or Publication Title:	Int. J. Mol. Sci.
Volume:	21
Number:	18
Date:	2020
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1422-0067
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROTEIN 6 JMJD6; LABEL-FREE; DOMAIN; PHOSPHATASE; RECEPTOR; U2AF65 Multiple languages Biochemistry & Molecular Biology; Chemistry, Multidisciplinary Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/32035