The RNA-binding landscape of HAX1 protein indicates its involvement in translation and ribosome assembly

Anna Balcerak, Ewelina Macech-Klicka, Maciej Wakula, Rafal Tomecki, Krzysztof Goryca, Malgorzata Rydzanicz, Mateusz Chmielarczyk, Malgorzata Szostakowska-Rodzos, Marta Wisniewska, Filip Lyczek, Aleksandra Helwak, David Tollervey, Grzegorz Kudla, Ewa A. Grzybowska*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

HAX1 is a human protein with no known homologues or structural domains. Mutations in the HAX1 gene cause severe congenital neutropenia through mechanisms that are poorly understood. Previous studies reported the RNA-binding capacity of HAX1, but the role of this binding in physiology and pathology remains unexplained. Here, we report the transcriptome-wide characterization of HAX1 RNA targets using RIP-seq and CRAC, indicating that HAX1 binds transcripts involved in translation, ribosome biogenesis, and rRNA processing. Using CRISPR knockouts, we find that HAX1 RNA targets 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. The 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.

Original languageEnglish
Article number2943
Number of pages22
Issue number19
Publication statusPublished - 20 Sept 2022

Keywords / Materials (for Non-textual outputs)

  • CRAC
  • HAX1
  • ribosome assembly
  • RIP-seq
  • RNA–protein binding
  • translation


Dive into the research topics of 'The RNA-binding landscape of HAX1 protein indicates its involvement in translation and ribosome assembly'. Together they form a unique fingerprint.

Cite this