Open AccessDistinct roles of hnRNPH1 low-complexity domains in splicing and transcription
Author(s) -
Ga Hye Kim,
Ilmin Kwon
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2109668118
Subject(s) - rna splicing , ribonucleoprotein , rna , rna binding protein , biogenesis , transcription (linguistics) , microbiology and biotechnology , biology , alternative splicing , heterogeneous ribonucleoprotein particle , chemistry , computational biology , genetics , gene , exon , linguistics , philosophy
Significance Phase separation of low-complexity (LC) domains appended to most RNA-binding proteins (RBPs) emerges as a principle underlying spatiotemporal protein recruitment. Yet, how LC domains regulate the function of RBPs in cells remains unclear. An alternative-splicing regulator, hnRNPH1, contains two LC domains (LC1 and LC2). Here, we show that phase separation of the LC1 can exert control over hnRNPH1 function in RNA-splicing possibly by facilitating interactions between hnRNPH1 and a variety of RBPs. In contrast, the LC2 lacking in vitro phase properties, is required for aberrant transcriptional activation in the context of fusion oncoproteins. These results have broad implications for understanding how phase separation contributes to distinct roles of LC domains in control of physiological as well as oncogenic functions.