TERT (Tetrahymena thermophila, O77448) — curation notes

Automated deep research was unavailable for this gene. The deep-research providers
configured in this repository could not be used (perplexity is not a registered provider;
falcon fails authentication; openai returns invalid_api_key). What follows is a manual
literature review compiled from the cached publications in publications/, the UniProt
flat file TERT-uniprot.txt, and QuickGO term lookups. No file named *-deep-research-*.md
was created.

1. Identity and architecture

2. Core molecular function: the catalytic subunit of a telomerase RNP

TERT is the protein half of a ribonucleoprotein; the RNA half (TER) supplies the template.
This is explicit in the founding Tetrahymena work:

So the activity is a property of the TERT+TER pair. TERT, however, is the subunit that carries
the RT active site and that determines template use — the discriminating result of
PMID:10944124 is that single substitutions in TERT change template boundaries, processivity
and nucleotide selectivity:

Catalytically this is an RNA-templated DNA polymerase (EC 2.7.7.49; Rhea:RHEA:22508 per
TERT-uniprot.txt), but one whose template is internal — which is exactly the distinction GO
captures with GO:0003720 telomerase activity (def.: "...using an internal RNA template that
encodes the telomeric repeat sequence", QuickGO). GO:0003964 and GO:0034061 are its
ancestors (QuickGO ancestor query), i.e. true but entailed.

3. Nucleic-acid binding by TERT

Telomerase RNA (TER). The TRBD is the high-affinity TER-binding module, and the TEN domain
adds non-sequence-specific RNA contact:

Telomeric DNA. Importantly, what TERT binds is the single-stranded 3′ telomeric primer,
not duplex telomeric repeat DNA. The TEN crystal structure paper is explicit:

This is the basis for proposing GO:0043047 single-stranded telomeric DNA binding
(a child of GO:0042162 telomeric repeat DNA binding, QuickGO) in place of the parent term.

4. The Tetrahymena holoenzyme — which parts are TERT's

The composition is Tetrahymena-specific and must not be read off human telomerase. From the
cached primary literature:

Division of labour that matters for annotation. High repeat-addition processivity and the
tether to the chromosome end are supplied by Teb1/p82 and p50, not by TERT:
PMID:19941821 and
PMID:23552895. So processivity-specific or telomere-recruitment-specific
terms belong to those subunits, not to TERT.

5. p65/TAP65 relationship (reviewed in parallel; do not duplicate here)

p65 is an assembly/architectural factor acting on TER, upstream of and within the RNP:

Annotation consequence: both TERT and p65 are legitimately part_of GO:0000333 telomerase catalytic core complex and part_of GO:0005697 telomerase holoenzyme complex. The
catalytic MF (GO:0003720) is TERT's, not p65's.

6. What is NOT supported in Tetrahymena (guard against human-telomerase import)

The following are well known for human TERT but have no support in the cached Tetrahymena
literature and must not be annotated here:

7. Localisation

UniProt records Nucleus {ECO:0000255|RuleBase:RU365061} and Chromosome, telomere {ECO:0000255|RuleBase:RU365061, ECO:0000269|PubMed:16462747} (TERT-uniprot.txt). Both are
biologically sound — telomerase acts on nuclear chromosome ends — but the Tetrahymena-specific
support is indirect (telomeric primer binding and in vivo telomere maintenance requirement
rather than a microscopy or ChIP experiment in the cached set). Note that Tetrahymena has two
nuclei; GO has GO:0031039 macronucleus and GO:0031040 micronucleus, and the cached papers
do not distinguish which compartment was assayed, so the generic GO:0005634 nucleus is as
precise as the available evidence allows. This is raised as a suggested question rather than
acted on.

8. Review decisions (summary)

GO term Action Why
GO:0003720 telomerase activity (4 IDA + 1 IEA) ACCEPT The defining function; EC 2.7.7.49 with four experimental references
GO:0005697 telomerase holoenzyme complex (5 IDA) ACCEPT Directly demonstrated by purification, EM and cryo-EM
GO:0000333 telomerase catalytic core complex (IEA) ACCEPT TERT+TER+p65 core is the structurally defined unit
GO:0007004 telomere maintenance via telomerase (IDA + IEA) ACCEPT The process TERT executes
GO:0070034 telomerase RNA binding (IDA + IEA) ACCEPT TRBD/TEN–TER contacts, structurally resolved
GO:0000781 chromosome, telomeric region (IEA) ACCEPT Site of action; holoenzyme is bridged to telomeres
GO:0005634 nucleus (IEA) ACCEPT Correct and as precise as the evidence allows
GO:0042162 telomeric repeat DNA binding (IDA + IEA) MODIFY → GO:0043047 TERT binds the single-stranded 3′ primer
GO:0034061 DNA polymerase activity (4 EXP + 1 IEA) TOO_GENERAL Strict ancestor of the accepted GO:0003720
GO:0003964 RNA-directed DNA polymerase activity (IEA) TOO_GENERAL Strict ancestor of GO:0003720
GO:0003677 DNA binding (IEA) TOO_GENERAL Strict ancestor of the telomeric DNA-binding term
GO:0000723 telomere maintenance (IEA) TOO_GENERAL Strict ancestor of the accepted GO:0007004

No NEW rows were proposed. The obvious candidates were tested and rejected:

No new GO term is needed: GO:0003720 already encodes the internal-template distinction that
makes telomerase special, so proposed_new_terms is empty.