Researchers at the University of Osaka in Japan have identified how cells sense temperature to coordinate the recovery of gene expression after heat stress, centering on membrane-free organelles called nuclear stress bodies that regulate the splicing of more than 400 pre-mRNAs during recovery from thermal stress.
The team found that a protein called CLK1 acts as the key regulator, controlled by a multi-step phosphorylation cycle: CLK1 is phosphorylated under normal conditions, dephosphorylated during heat stress by the enzyme PP1 (itself activated by the reversible thermosensor PPP1R2), and then rephosphorylated during recovery by the enzyme RIOK2. These changes determine whether CLK1 is excluded from or recruited to nuclear stress bodies, and therefore whether temperature-dependent splicing is switched on.
“Nuclear stress bodies are membrane-free organelles that regulate the splicing of more than 400 pre-mRNAs during recovery from thermal stress… However, it remains unclear how these bodies recruit key regulators in response to changing temperatures,” said lead author Tsuyoshi Ueno.
“Our findings show that a multi-component heat-sensing mechanism coordinates CLK1 localization to nuclear stress bodies,” Ueno added.
“The results revealed a simple and elegant regulatory system… CLK1 is phosphorylated at a specific serine residue under normal conditions, dephosphorylated during heat stress, and rephosphorylated during recovery; these changes control whether CLK1 is excluded from or recruited to nuclear stress bodies,” said senior author Tetsuro Hirose.
Journal: Molecular Cell
DOI: 10.1016/j.molcel.2026.06.034
Article Title: Thermo-Sensing Mechanisms of Splicing Control by Nuclear Stress Bodies
Publication Date: 16-Jul-2026
Funding: Japan Society for the Promotion of Science, Japan Agency for Medical Research and Development, Japan Science and Technology Agency
Source: EurekAlert