Unfolded protein responses in C. elegans

Reviewing GO annotations for 18 genes of the ER and mitochondrial stress responses

AI Gene Review · projects/CAEEL_UPR_STRESS · 2026

Bottom line

  • ER stress is sensed by IRE-1, PEK-1 and ATF-6; mitochondrial stress by ATFS-1 with DVE-1, UBL-5 and chromatin regulators.
  • We reviewed every GO annotation on 18 genes: 421 rows, 344 ACCEPT, 13 MODIFY, 5 REMOVE, 21 NEW.
  • Four of the five removals fix a specific error, e.g. protein tag activity on UBL-5, which cannot be conjugated; the HSP-60 one overrules an IPI row from an abstract only and is tentative.

Why the worm

  • Non-cell-autonomous UPR was found here: neurons can switch on stress responses in the intestine.
  • hsp-4::GFP and hsp-6::GFP are standard in vivo reporters.
  • ATF-6 deletion extends lifespan through ER-mitochondrial calcium signalling.
  • Test: does GO keep sensors, transcription factors and reporter chaperones apart?

The two responses and the 18 genes

Actions per gene

The five removals

Gene Term Evidence Why
ubl-5 protein tag activity IBA no C-terminal di-Gly; acts non-covalently
hsp-60 RNA Pol II TF binding IPI abstract shows DVE-1 on the hsp-60 promoter; full text unseen, so tentative
jmjd-3.1 RNA Pol II cis-regulatory DNA binding IBA no intrinsic DNA-binding domain
met-2 histone H3K36 methyltransferase activity IMP SETDB1-family enzymes are H3K9-specific
ire-1 unfolded protein binding IBA obsolete term; sensing is not chaperone binding

From review.reason in genes/worm/<gene>/<gene>-ai-review.yaml.

What was added

  • MET-2: histone H3K9 dimethyltransferase activity, constitutive heterochromatin formation, transposable element silencing (IMP).
  • UBL-5: splicing factor binding and transcription coactivator activity (IDA).
  • ATF-4: integrated stress response signalling (IMP); ATF-6: ER calcium ion homeostasis (IMP).
  • HSP-6: mitochondrial matrix (IDA), protein import into the matrix (ISS).

Status and next steps

  • ✅ 18/18 gene reviews and the pathway summary; atfs-1 and hsp-4 shared with CAEEL_MITOPHAGY and CAEEL_PROTEOSTASIS.
  • ⬜ Listed but not reviewed: atf-5, abu-8, abu-11, jmjd-1.2 (hsp-3 has a review outside this project).

Read more: projects/CAEEL_UPR_STRESS.md · projects/CAEEL_UPR_STRESS/CAEEL_UPR_STRESS-pathway.md · genes/worm/<gene>/