中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (2): 259-260.doi: 10.4103/1673-5374.265549

• 观点:退行性病与再生 • 上一篇    下一篇

内含子保留增加与阿尔茨海默病有关

  

  • 出版日期:2020-02-15 发布日期:2020-05-25

Increased intron retention is linked to Alzheimer’s disease

Chin-Tong Ong, Swarnaseetha Adusumalli   

  1. Temasek Life Sciences Laboratory, Department of Biological Sciences, National University of Singapore, Singapore
  • Online:2020-02-15 Published:2020-05-25
  • Contact: Chin-Tong Ong, PhD, chintong@tll.org.sg.
  • Supported by:
    This work was supported by core funding provided by Temasek Life Sciences Laboratory.

摘要: orcid: 0000-0002-5450-4760 (Chin-Tong Ong)
         0000-0003-0704-9061 (Swarnaseetha Adusumalli)

Abstract: AD is an age-related neurodegenerative disorder with pathological accumulation of amyloid plaque (Masters et al., 2015), which can be classified into familial and sporadic form. In familial AD, mutations in genes encoding either amyloid precursor protein or presenilin (PS1 and PS2) cause overproduction of amyloid-42 molecules and early onset of dementia. Late-onset sporadic AD, which accounts for majority of the cases (> 95%), is characterized by high degree of genetic and pathological heterogeneity. Although aging and genetic variants are two risks factors for sporadic AD, it remains unclear how epigenetic alterations during aging may contribute to its etiology. To determine the transcriptional changes that are associated with aging, we analyzed the transcriptome of head or brain tissues isolated at different ages from adult Drosophila, mice and human (Adusumalli et al., 2019). We observed an increase in the level of intron retention (IR) in the mRNA transcripts during aging across different species. These retained introns share highly conserved features and surprisingly, do not affect the expression level of their mRNA transcripts. As many age-dependent IR mRNA transcripts overlapped with curated AD genes, we further compared the IR patterns in the frontal cortex and cerebellum isolated from large AD cohorts with their age-matched controls. Consistent with reports of aberrant splicing in AD (Tollervey et al., 2011; Bai et al., 2013; Raj et al., 2018), we found a significant increase in the rate of IR at genes that are involved in RNA processing and protein homeostasis in AD samples. Furthermore, many of these IR genes showed significant changes in their protein levels when compared to age-matched controls. Taken together, our findings suggest that increased IR is a transcriptional signature that is conserved across species during aging and may be linked to AD progression.