TOR-dependent regulation of the yeast homolog of the juvenile Batten Disease-associated gene CLN3
Authors:Vijaykumar Pillalamarri1, Samuel W.M. Gatesy1, Amanda E. Grassel1, Lucienna Wolf1, Justin P. Whalley2 and David M. Mueller1,*
doi: 10.15698/mic2026.03.872
Volume 13, pp. 131 to 147, published 11/03/2026.
1 Discipline of Biochemistry and Molecular Biology, Center for Genetic Diseases, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL, 60064, United States of America. 2 Discipline of Microbiology and Immunology, Center for Cancer Cell Biology, Immunology, and Infection, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL, 60064, United States of America.
Keywords:
BTN1, CLN3, Batten Disease, translational regulation, amino acid starvation
Corresponding Author(s):
Conflict of interest statement:
The authors declare no conflict of interest.
Please cite this article as:
Vijaykumar Pillalamarri, Samuel Gatesy, Amanda E. Grassel, Lucienna Wolf, Justin P. Whalley, and David M. Mueller (2026). TOR-dependent regulation of the yeast homolog of the juvenile Batten Disease-associated gene CLN3. Microbial Cell 13: 131-147. doi: 10.15698/mic2026.03.872
© 2026 Pillalamarri et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
The Juvenile form of Batten disease is a neurodegenerative disease with symptoms starting in the first decade and ending in death in the third decade of life. The gene defective in this form of Batten disease, CLN3, is conserved in eukaryotes, suggesting that the gene product serves a basic function in the cell, though the function is unknown. We have investigated the expression and regulation of the yeast homolog BTN1. Reanalysis of publicly available gene expression data suggests that transcription of BTN1 increases in response to oxidative stress, treatment with rapamycin or arsenate, amino acid starvation, and sporulation conditions. Similar to GCN4, there are upstream open reading frames (uORF) in front of BTN1, suggesting translational regulation. We developed reporter strains in which the HIS3 open reading frame replaced that of the BTN1 gene, with and without the uORFs. These reporters show that one or more of the uORFs decrease the expression of the HIS3 reporter. When expressed in the reporter strain using a high copy vector, GCN3, tRNAArg, and tRNALeu, increase expression, suggesting the involvement of the TORC1 pathway. BIT61 abuts BTN1 but is encoded on the opposite strand; 3’ RACE analysis indicates that the mRNA of BIT61 overlaps with that of BTN1. BIT61 is involved in the TORC2 pathway, which interacts with the TORC1 pathway, suggesting a possible cis-acting mechanism of coregulation. Lastly, we demonstrate that a yeast strain with a null mutation in BTN1 is sensitive to selective amino acid starvation, further supporting the association of BTN1 with TORC1.