Disordered regions of mixed lineage leukemia 4 (MLL4) protein are capable of RNA binding

TY - JOUR

T1 - Disordered regions of mixed lineage leukemia 4 (MLL4) protein are capable of RNA binding

AU - Szabó, Beáta

AU - Murvai, Nikoletta

AU - Abukhairan, Rawan

AU - Schád, Éva

AU - Kardos, József

AU - Szeder, Bálint

AU - Buday, László

AU - Tantos, Ágnes

N1 - Publisher Copyright: © 2018 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2018/11

Y1 - 2018/11

N2 - 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.

AB - 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.

KW - Histone lysine methyltransferase

KW - HOTAIR

KW - IncRNA

KW - Intrinsically disordered protein

KW - Leukemia

KW - MEG3

KW - MLL proteins

KW - MLL4

KW - RNA binding

UR - https://www.scopus.com/pages/publications/85056275009

U2 - 10.3390/ijms19113478

DO - 10.3390/ijms19113478

M3 - Article

C2 - 30400675

AN - SCOPUS:85056275009

SN - 1661-6596

VL - 19

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 11

M1 - 3478

ER -