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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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Emerging roles of alternative cleavage and polyadenylation (APA) in human disease

Prakash Dharmalingam1, Rajasekaran Mahalingam2, Hari Krishna Yalamanchili3,4,5

  • 1Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical & Technical Sciences, Saveetha University, Chennai, India.

Journal of Cellular Physiology
|August 11, 2021
PubMed

Insights

Alternative polyadenylation (APA) generates diverse mRNA transcripts, impacting gene regulation and disease. This review explores the crucial roles of the APA machinery in various human diseases, highlighting its pathobiological significance.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Messenger RNA (mRNA) undergoes maturation, involving 3'-end cleavage and poly(A) tail addition, crucial for mRNA stability and function.
  • Alternative polyadenylation (APA) involves differential cleavage at multiple polyadenylation sites, producing mRNA variants and influencing biological processes.
  • While APA's role in gene regulation and diseases like cancer is studied, the function of core APA machinery in disease remains largely unexplored.

Purpose of the Study:

  • To review the functions of the core alternative polyadenylation (APA) machinery and related factors in the context of human diseases.
  • To consolidate current knowledge on APA's involvement in the pathobiology of diverse conditions.
  • To provide a foundation for understanding APA's emerging role in disease.

Main Methods:

  • Literature review focusing on alternative polyadenylation (APA) machinery.
  • Analysis of APA's role in gene regulation, cell proliferation, senescence, and disease.
  • Synthesis of findings related to APA in brain diseases, cardiac failure, pulmonary fibrosis, cancer, and infectious diseases.

Main Results:

  • Alternative polyadenylation (APA) is prevalent, with 60%-70% of human genes possessing multiple APA sites.
  • APA plays significant roles in gene regulation, cell proliferation, senescence, and is implicated in various human diseases.
  • The functions of core APA machinery in disease pathogenesis are not well-understood, despite extensive research on regulatory factors.

Conclusions:

  • Alternative polyadenylation (APA) is a key mechanism influencing mRNA diversity and cellular functions.
  • Understanding the role of APA machinery in diseases like cancer, cardiac failure, and neurological disorders is critical.
  • This review highlights APA's emerging importance in the pathobiology of human diseases, offering avenues for future research.
Keywords:
3'-UTRRNA binding proteinsRNA biologyalternative cleavage and polyadenylationmRNA maturationpolyadenylation

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