NBDY (NoBody; A0A0U1RRE5) review notes

2026-09-30 session

68-aa intrinsically disordered microprotein encoded by a smORF in the lncRNA-annotated
locus LINC01420 (Xq). UniProt: "Was previously thought to be non-coding but has been
shown to be translated and functional." Whole chain predicted disordered (MobiDB-lite);
C-terminal proline-rich region.
Conserved in mammals only; no homology to known domains
PMID:27918561.

Affinity purification-MS: "only twelve proteins were specifically enriched >2-fold by
NoBody, all of which are components of mRNA decapping and 5'-to-3' mRNA decay complexes".
Direct binding to EDC4: GST pull-down plus benzophenone photo-crosslinking
PMID:27918561.
Residues 22-41 necessary and sufficient; alanine scan: L30 and W34 required.
EDC4 knockdown abolishes co-purification of other decapping factors
PMID:27918561.
P-bodies: overexpression disperses P-bodies (not degradation of components), requires the
peptide not the RNA; siRNA knockdown increases P-bodies 1.5-2x
PMID:27918561.
Localization: at low expression co-localizes with EDC4 in P-bodies
PMID:27918561.
NMD substrate (Calu-6 p53 mRNA): knockdown DECREASED, overexpression INCREASED steady-state
p53 mRNA. Authors explicitly say decay rate not measured
PMID:27918561
and interpret as negative regulation of decay
PMID:27918561.
=> The GOA IDA "nuclear-transcribed mRNA catabolic process" (GO:0000956) is based on this
steady-state measurement. NBDY does not catalyse any step of mRNA breakdown; the direction of
the effect (if anything) is inhibitory. Not participation.

Endogenous NBDY binds EDC4 WD40 domain directly; DCP1A EVH1 binds NBDY C-terminal polyproline.
NBDY KO HEK293T: 3x more P-bodies, rescued by re-expression; decreased viability.
TimeLapse-seq: >1400 half-lives changed (1200 stabilized, 226 destabilized)
PMID:33059440.
DCP2 substrates stabilized OR destabilized depending on 5' UTR length; requires EDC4
interaction (W34A).
NBDY does not change in vitro decapping activity of immunopurified complex
PMID:33059440.
Non-DCP2 targets stabilized indirectly through reduced synthesis of NMD factor transcripts.
=> Best process term for this: GO:0043488 regulation of mRNA stability ("Includes processes
that both stabilize and destabilize mRNAs"). Used as MODIFY replacement for GO:0000956.

NBDY + RNA undergo LLPS in vitro (complex coacervation with polyU; needs PEG crowder;
critical concentration 150 uM - far above cellular).
Phosphorylation: T40 at G2/M (CDK-dependent), S61 after EGF (PKC; PKCalpha phosphorylates in
vitro). Non-phosphorylatable mutants abrogate mitotic / EGF-induced P-body loss.
PMID:34346674.
Strengthens GO:0010607 negative regulation of cytoplasmic mRNA processing body assembly.
In vitro RNA LLPS not proposed as NEW (reductionist, high concentration; RNA binding not
shown to be sequence-specific or relevant in cells).

requires EDC4 N-terminal WD40 region. Supports EDC4 binding.

NBDY 22-41 binds EDC4 C-terminal domain directly and competes EDC4-EDC4 self-association;
disrupts P-bodies without affecting tethered mRNA decay
PMID:40360209.
Further argues against NBDY participating in mRNA catabolism per se.

relevance, computational only.

P-body IDA/IEA: ACCEPT.
GO:0010607 IDA: ACCEPT (core).
GO:0000956 IDA: MODIFY -> GO:0043488 regulation of mRNA stability.
protein binding IPI (EDC4, DCP1A): REMOVE per repo protein-binding policy (interactions are real
and direct, but the term is uninformative; no specific MF term available for a non-enzymatic
EDC4-binding regulator). Removal does not dispute the interactions.
No NEW annotations. Considered RNA decapping complex (GO:0098745) membership - left as question.
Core MF: no suitable GO MF; leave molecular_function unset.