Importance of the long non-coding RNA (lncRNA) transcript HULC for the regulation of phenylalanine hydroxylase and treatment of phenylketonuria.

Chunru Lin, Yajuan Li, Eric Zhang, François Feillet, Shuxing Zhang, Nenad Blau

Journal: Molecular genetics and metabolism 2022;135(3):171-178

PMID: 35101330

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Abstract

More than 1280 variants in the phenylalanine hydroxylase (PAH) gene are responsible for a broad spectrum of phenylketonuria (PKU) phenotypes. While the genotype-phenotype correlation is reaching 88%, for some inconsistent phenotypes with the same genotype additional factors like tetrahydrobiopterin (BH), the PAH co-chaperone DNAJC12, phosphorylation of the PAH residues or epigenetic factors may play an important role. Very recently an additional player, the long non-coding RNA (lncRNA) transcript HULC, was described to regulate PAH activity and enhance residual enzyme activity of some PAH variants (e.g., the most common p.R408W) by using HULC mimics. In this review we present an overview of the lncRNA function and in particular the interplay of the HUCL transcript with the PAH and discuss potential applications for the future treatment of some PKU patients.

Address: Department of Molecular and Cellular Oncology, Division of Basic Science Research, The University of Texas, MD Anderson Cancer Center, Houston, TX, United States of America.; Department of Experimental Therapeutics, The University of Texas, MD Anderson Cancer Center, Houston, TX, United States of America.; INSERM, U1256, NGERE - Nutrition, Genetics, and Environmental Risk Exposure, University of Lorraine, Nancy, France; Pediatric Department Reference Center for Inborn Errors of Metabolism Children University Hospital Nancy, Nancy, France.; Division of Metabolism, University Children's Hospital Zürich, Zurich, Switzerland. Electronic address: [email protected].

DOI: 10.1016/j.ymgme.2022.01.004

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https://medlineplus.gov/phenylketonuria.html

MeSH Terms: Humans, Mutation, Phenotype, Phenylalanine Hydroxylase, Phenylketonurias, RNA, Long Noncoding