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

**Beáta Szabó 1, Nikoletta Murvai 1, Rawan Abukhairan 1, Éva Schád 1, József Kardos 2, Bálint Szeder 1, László Buday <sup>1</sup> and Ágnes Tantos 1,\***


Received: 30 September 2018; Accepted: 2 November 2018; Published: 5 November 2018

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