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Record W4413060253 · doi:10.1101/2025.07.11.664446

Alpha satellite RNA marks the perinucleolar compartment and represses ribosomal RNA expression in naïve human embryonic stem cells

2025· preprint· en· W4413060253 on OpenAlexaff
Kirti Mittal, Lamisa Ataei, Miguel Ramalho‐Santos

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Research and Splicing
Canadian institutionsUniversity of TorontoLunenfeld-Tanenbaum Research InstituteMount Sinai Hospital
Fundersnot available
KeywordsChromatinBiologyRNASmall nuclear RNACell biologyMolecular biologyTranscription (linguistics)Non-coding RNARibosomal RNAGeneticsGene

Abstract

fetched live from OpenAlex

Abstract While most newly synthesized RNA is exported to the cytoplasm, a portion of non-coding RNA is retained in the nucleus and remains highly associated with chromatin. The strong binding of this RNA fraction to insoluble chromatin impairs its recovery in standard transcriptomic studies. Therefore, the landscape and potential functions of chromatin-associated RNAs are poorly understood. Recent studies indicate that chromatin-associated transcripts can have regulatory roles, particularly during mammalian development. Here we compare the dynamics of cytoplasmic versus chromatin-bound transcriptomes of naïve and primed human embryonic stem cells (hESCs), as well as fibroblasts. We found a remarkable enrichment for RNA transcribed from alpha satellite repeat (ALR) in the chromatin fraction of naïve hESCs, compared to primed hESCs. The co-localization and interaction of ALR RNA with Polypyrimidine Tract Binding Protein 1 (PTBP1) protein indicate that ALR RNA foci mark the perinucleolar compartment (PNC), a nuclear sub-compartment previously thought to be exclusive to cancer cells. Knockdown of ALR RNA leads to dispersion of PTBP1 foci, up-regulation of ribosomal RNA and global hypertranscription in naïve hESCs. In contrast, loss of PTBP1 does not disturb ALR RNA localization, indicating that ALR is upstream in the hierarchy of organization of the PNC in hESCs. These results reveal a role for ALR RNA in nuclear compartmentalization and tuning rRNA synthesis in naïve hESCs. Moreover, this study opens new avenues to dissect the function of ALR RNA and the PNC in cancer contexts.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.247
Teacher spread0.234 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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