論文 - 詳細
| RRC ID | 73984 |
|---|---|
| 著者 | Komuro R, Honda Y, Yanaizu M, Nagahama M, Kino Y. |
| タイトル | Alzheimer's Disease-Associated Alternative Splicing of CD33 Is Regulated by the HNRNPA Family Proteins. |
| ジャーナル | Cells |
| Abstract |
Genetic variations of CD33 have been implicated as a susceptibility factor of Alzheimer's disease (AD). A polymorphism on exon 2 of CD33, rs12459419, affects the alternative splicing of this exon. The minor allele is associated with a reduced risk of AD and promotes the skipping of exon 2 to produce a shorter CD33 isoform lacking the extracellular ligand-binding domain, leading to decreased suppressive signaling on microglial activity. Therefore, factors that regulate the splicing of exon 2 may alter the disease-associated properties of CD33. Herein, we sought to identify the regulatory proteins of CD33 splicing. Using a panel of RNA-binding proteins and a human CD33 minigene, we found that exon 2 skipping of CD33 was promoted by HNRNPA1. Although the knockdown of HNRNPA1 alone did not reduce exon 2 skipping, simultaneous knockdown of HNRNPA1 together with that of HNRNPA2B1 and HNRNPA3 promoted exon 2 inclusion, suggesting functional redundancy among HNRNPA proteins. Similar redundant regulation by HNRNPA proteins was observed in endogenous CD33 of THP-1 and human microglia-like cells. Although mouse Cd33 showed a unique splicing pattern of exon 2, we confirmed that HNRNPA1 promoted the skipping of this exon. Collectively, our results revealed novel regulatory relationships between CD33 and HNRNPA proteins. |
| 巻・号 | 12(4) |
| 公開日 | 2023-2-13 |
| DOI | 10.3390/cells12040602 |
| PII | cells12040602 |
| PMID | 36831269 |
| PMC | PMC9954446 |
| MeSH | Alternative Splicing* Alzheimer Disease* / metabolism Animals Exons Humans Mice Protein Isoforms / metabolism RNA Splicing Sialic Acid Binding Ig-like Lectin 3* / metabolism |
| IF | 4.366 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293(RCB1637) THP-1(RCB1189) |