RT Journal Article
SR Electronic
T1 The RNA-binding landscape of HAX1 protein indicates its involvement in ribosome biogenesis and translation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.14.476349
DO 10.1101/2022.01.14.476349
A1 Anna Balcerak
A1 Ewelina Macech-Klicka
A1 Maciej Wakula
A1 Rafal Tomecki
A1 Krzysztof Goryca
A1 Malgorzata Rydzanicz
A1 Mateusz Chmielarczyk
A1 Malgorzata Szostakowska-Rodzos
A1 Marta Wisniewska
A1 Filip Lyczek
A1 Aleksandra Helwak
A1 David Tollervey
A1 Grzegorz Kudla
A1 Ewa A. Grzybowska
YR 2022
UL http://biorxiv.org/content/early/2022/06/20/2022.01.14.476349.abstract
AB HAX1 is a human protein with no known homologues or structural domains, mutations in which cause severe congenital neutropenia through mechanisms that are poorly understood. Previous studies reported RNA-binding capacity of HAX1, but the role of this binding in physiology and pathology remains unexplained. Here we report transcriptome-wide characterization of HAX1 RNA targets using RIP-seq and CRAC, indicating that HAX1 binds transcripts involved in ribosome biogenesis and rRNA processing. Using CRISPR knockouts we find that RNA targets of HAX1 partially overlap with transcripts downregulated in HAX1 KO, implying a role in mRNA stabilization. Gene ontology analysis demonstrated that genes differentially expressed in HAX1 KO (including genes involved in ribosome biogenesis and translation) are also enriched in a subset of genes whose expression correlates with HAX1 expression in four analyzed neoplasms. Functional connection to ribosome biogenesis was also demonstrated by gradient sedimentation ribosome profiles, which revealed differences in the small subunit:monosome ratio in HAX1 WT/KO. We speculate that changes in HAX1 expression may be important for the etiology of HAX1-linked diseases through dysregulation of translation.Competing Interest StatementThe authors have declared no competing interest.