The GUL-1 Protein Binds Multiple RNAs Involved in Cell Wall Remodeling and Affects the MAK-1 Pathway in Neurospora crassa

Inbal Herold; Avihai Zolti; Marisela Garduño-Rosales; Zheng Wang; Francesc López-Giráldez; Rosa R Mouriño-Pérez; Jeffrey P Townsend; Igor Ulitsky; Oded Yarden

doi:10.3389/ffunb.2021.672696

The GUL-1 Protein Binds Multiple RNAs Involved in Cell Wall Remodeling and Affects the MAK-1 Pathway in Neurospora crassa

Front Fungal Biol. 2021 Apr 16:2:672696. doi: 10.3389/ffunb.2021.672696. eCollection 2021.

Authors

Affiliations

¹ Department of Plant Pathology and Microbiology, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
² Departamento de Microbiología, CICESE (Centro de Investigación Científica y Educación Superior de Ensenada), Ensenada, Mexico.
³ Department of Biostatistics, Yale University, New Haven, CT, United States.
⁴ Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT, United States.
⁵ Yale Center for Genome Analysis, Department of Genetics, Yale University, New Haven, CT, United States.
⁶ Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.

Abstract

The Neurospora crassa GUL-1 is part of the COT-1 pathway, which plays key roles in regulating polar hyphal growth and cell wall remodeling. We show that GUL-1 is a bona fide RNA-binding protein (RBP) that can associate with 828 "core" mRNA species. When cell wall integrity (CWI) is challenged, expression of over 25% of genomic RNA species are modulated (2,628 mRNAs, including the GUL-1 mRNA). GUL-1 binds mRNAs of genes related to translation, cell wall remodeling, circadian clock, endoplasmic reticulum (ER), as well as CWI and MAPK pathway components. GUL-1 interacts with over 100 different proteins, including stress-granule and P-body proteins, ER components and components of the MAPK, COT-1, and STRIPAK complexes. Several additional RBPs were also shown to physically interact with GUL-1. Under stress conditions, GUL-1 can localize to the ER and affect the CWI pathway-evident via altered phosphorylation levels of MAK-1, interaction with mak-1 transcript, and involvement in the expression level of the transcription factor adv-1. We conclude that GUL-1 functions in multiple cellular processes, including the regulation of cell wall remodeling, via a mechanism associated with the MAK-1 pathway and stress-response.

Keywords: COT-1; GUL-1; MAPK; Nikkomycin; RNA-binding protein; cell wall integrity pathway; cell wall remodeling.