T16G12.6/IMPORTIN 13-mediated cytoplasm-to-nucleus transport of the THAP transcription factor LIN-15B controls autophagy and lysosome function in C. elegans.

Transcriptional regulation of genes involved in the macroautophagy/autophagy-lysosome pathway acts as an important mechanism for controlling autophagy activity. The factors that globally regulate autophagy activity at the transcriptional level during C. elegans development remain unknown. Here we showed that the THAP domain-containing transcription factor LIN-15B modulates autophagy activity during C. elegans development. Loss of function of lin-15B suppresses the autophagy defect caused by impaired autophagosome maturation and promotes lysosome biogenesis and function. LIN-15B maintains the repressed state of genes involved in the autophagy pathway. Accordingly, loss of function of lin-15B upregulates a plethora of genes involved in autophagosome formation and maturation as well as lysosome biogenesis and function. The cytoplasm-to-nucleus translocation of LIN-15B is mediated by the T16G12.6/IMPORTIN 13/IPO-13 receptor and modulated by nutrient status. Our study uncovers that LIN-15B integrates environmental cues into transcriptional control of a network of genes involved in autophagy in C. elegans.Abbreviations: ATG: autophagy related; DIC: differential interference contrast; EPG: ectopic PGL granules; ER: endoplasmic reticulum; FOXO: forkhead box O; GFP: green fluorescent protein; SQST-1: SeQueSTosome related 1; SynMuv: synthetic multivulva; IPO-13: importin 13; TFEB: transcription factor EB.