HuD interacts with survival motor neuron protein and can rescue spinal muscular atrophy-like neuronal defects
Bibliographic record
Abstract
Spinal muscular atrophy is an autosomal-recessive neuromuscular disease caused by disruption of the survival of motor neuron (SMN) gene, which promotes cytoplasmic assembly of the splicing core machinery. It remains unclear how a deficiency in SMN results in a disorder leading to selective degeneration of lower motor neurons. We report here that SMN interacts with RNA-binding protein HuD in neurites of motorneuron-derived MN-1 cells. This interaction is mediated through the Tudor domain of SMN and, importantly, naturally occurring Tudor mutations found in patients with severe spinal muscular atrophy (SMA) completely abrogate the interaction, underscoring its relevance to the disease process. We also characterized a regulatory pathway involving coactivator-associated arginine methyltransferase 1 (CARM1) and HuD. Specifically, we show that CARM1 expression is rapidly downregulated, at the protein level, following induction of differentiation through retinoid and neurotrophic signaling. Using purified proteins, we demonstrate that methylation of HuD by CARM1 reduces its interaction with the p21(cip1/waf1) mRNA, showing that CARM1 can directly influence RNA-binding activity. We further demonstrate that this CARM1-dependent regulatory switch mainly controls the activity of HuD in promoting cell-cycle exit, whereas the interaction between HuD and SMN is required for proper recruitment of HuD and its mRNA targets in neuronal RNA granules. Finally, we were able to rescue SMA-like defects in a hypomorphic Smn knockdown MN-1 cell line through overexpression of HuD. Together, these findings extend our understanding of specific role(s) of SMN in motor neurons and provide crucial insights into potential new avenues for SMA therapeutic strategies.
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 imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".