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Int J Mol Sci. 2018 Nov 5;19(11). pii: E3478. doi: 10.3390/ijms19113478.

Disordered Regions of Mixed Lineage Leukemia 4 (MLL4) Protein Are Capable of RNA Binding.

Author information

1
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1117 Budapest, Hungary. szabo.beata@ttk.mta.hu.
2
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1117 Budapest, Hungary. murvai.nikoletta@ttk.mta.hu.
3
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1117 Budapest, Hungary. rawan.abukhairan@ttk.mta.hu.
4
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1117 Budapest, Hungary. schad.eva@ttk.mta.hu.
5
ELTE NAP Neuroimmunology Research Group, Department of Biochemistry, Eötvös Loránd University, H-1117 Budapest, Hungary. kardos@elte.hu.
6
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1117 Budapest, Hungary. szeder.balint@ttk.mta.hu.
7
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1117 Budapest, Hungary. buday.laszlo@ttk.mta.hu.
8
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1117 Budapest, Hungary. tantos.agnes@ttk.mta.hu.

Abstract

Long non-coding RNAs (lncRNAs) are emerging as important regulators of cellular processes and are extensively involved in the development of different cancers; including leukemias. As one of the accepted methods of lncRNA function is affecting chromatin structure; lncRNA binding has been shown for different chromatin modifiers. Histone lysine methyltransferases (HKMTs) are also subject of lncRNA regulation as demonstrated for example in the case of Polycomb Repressive Complex 2 (PRC2). Mixed Lineage Leukemia (MLL) proteins that catalyze the methylation of H3K4 have been implicated in several different cancers; yet many details of their regulation and targeting remain elusive. In this work we explored the RNA binding capability of two; so far uncharacterized regions of MLL4; with the aim of shedding light to the existence of possible regulatory lncRNA interactions of the protein. We demonstrated that both regions; one that contains a predicted RNA binding sequence and one that does not; are capable of binding to different RNA constructs in vitro. To our knowledge, these findings are the first to indicate that an MLL protein itself is capable of lncRNA binding.

KEYWORDS:

HOTAIR; MEG3; MLL proteins; MLL4; RNA binding; histone lysine methyltransferase; intrinsically disordered protein; leukemia; lncRNA

PMID:
30400675
DOI:
10.3390/ijms19113478
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