MicroRNA Degradation Project Sources

This file tracks the seed papers that define project scope. It is intentionally smaller than a full
literature review. New papers from Chris should be appended here first, and only then used to widen
the review queue.

P0: Anchor Mechanism

Source	Why it matters now	Current effect on scope
Farnung et al. 2026, "The E3 ubiquitin ligase mechanism specifying targeted microRNA degradation" (Nature)	Direct biochemical and cryo-EM mechanism for trigger-dependent AGO recognition by the ZSWIM8-CUL3 ligase with ELOB, ELOC, and ARIH1	Defines the phase-1 queue as a TDMD machinery project, not a generic miRNA turnover project
Shi et al. 2020, "The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation" (Science)	Establishes ZSWIM8 ligase requirement for TDMD and expands the biological relevance across mammals, flies, and nematodes	Justifies ZSWIM8 as the central project anchor
Han et al. 2020, "A ubiquitin ligase mediates target-directed microRNA decay independently of tailing and trimming" (Science)	Independent TDMD mechanism paper showing that ZSWIM8-dependent decay does not require tailing and trimming to be the core explanation	Keeps TUT and trimming pathways out of phase-1 core scope

P1: Endogenous Trigger Biology

Source	Why it matters now	Current effect on scope
Kleaveland et al. 2018, "A Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain" (Cell)	Canonical endogenous CYRANO-miR-7 example linking TDMD to mammalian brain biology	Track CYRANO as context, but do not add ncRNA jobs to the phase-1 queue
Bitetti et al. 2018, "MicroRNA degradation by a conserved target RNA regulates animal behavior" (Nature Structural & Molecular Biology)	NREP example with in vivo phenotype; useful for distinguishing validated endogenous trigger biology from speculative trigger predictions	Track NREP as context and later regulator-focused expansion
Ghini et al. 2018, "Endogenous transcripts control miRNA levels and activity in mammalian cells by target-directed miRNA degradation" (Nature Communications)	SERPINE1 establishes an endogenous protein-coding trigger transcript in mammalian cells	Supports a separate "trigger-bearing transcript" context list without turning those genes into phase-1 review jobs
Li et al. 2023, "Screening of Drosophila microRNA-degradation sequences reveals Argonaute1 mRNA's role in regulating miR-999" (Nature Communications)	Useful comparative Drosophila example and a reminder that trigger-bearing transcripts can be physiologically important	Comparative layer, not part of the initial human queue
Lin et al. 2026, "mRNA 3' UTRs direct microRNA degradation to participate in imprinted gene networks and regulate growth" (Genes & Development)	Expands the validated mouse trigger list to ATP6V1G1, LPAR4, PLAGL1, and LRRC58	Track these genes as regulators/context only unless a later subproject is explicitly about trigger-bearing transcripts

P2: Deferred Expansion

Source	Why it matters now	Current effect on scope
Yang et al. 2020, "AGO-bound mature miRNAs are oligouridylated by TUTs and subsequently degraded by DIS3L2" (Nature Communications)	Strong evidence for a miRNA turnover branch involving tailing and DIS3L2	Keep this branch as phase-2 expansion rather than mixing it into the phase-1 TDMD machinery queue

Intake Rule

• If a new paper directly changes the identity of the dedicated TDMD machinery, update genes.csv and fetch_queue.csv.
• If a new paper adds trigger RNAs or trigger-bearing transcripts, update this file and the context-regulator section of MIRNA_DEGRADATION.md first.
• Do not widen the review queue just because a gene's transcript contains a TDMD trigger site.