Alternative polyadenylation: An enigma of transcript length variation in health and disease

Neeraja K Mohanan1,2, Feba Shaji1,3, Ganesh R Koshre1,2

  • 1Cardiovascular and Diabetes Biology Group, Rajiv Gandhi Centre for Biotechnology, Trivandrum, India.

Insights

Alternative polyadenylation (APA) generates diverse mRNA transcripts from single genes, impacting protein diversity and human diseases. Targeting APA regulators offers therapeutic potential for diseases like cancer.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Alternative polyadenylation (APA) is a key RNA processing event.
  • APA generates mRNA variants with different 3'-UTR lengths from a single gene.
  • These variations influence mRNA stability, translation, localization, and protein function.

Purpose of the Study:

  • To review the occurrence and mechanisms of APA.
  • To explore the consequences of APA-driven transcript length variation in human diseases.
  • To highlight the therapeutic potential of targeting APA regulators.

Main Methods:

  • Literature review of APA mechanisms and disease associations.
  • Analysis of the relationship between 3'-UTR length and protein expression.
  • Examination of the role of RNA processing factors in disease-associated APA.

Main Results:

  • APA is a significant regulatory mechanism in human disease pathophysiology.
  • Changes in 3'-UTR length due to APA can alter protein expression, though this relationship is complex.
  • Core RNA processing factors, including poly(A) polymerases, are involved in disease-associated APA site selection.

Conclusions:

  • APA contributes to mRNA and protein diversification, playing a role in human diseases.
  • Understanding APA mechanisms is crucial for deciphering disease pathology.
  • Targeting APA regulators presents a promising therapeutic strategy for conditions such as cancer drug resistance.

Related Concept Videos

RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
57.8K
Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
22.0K
Translation01:31

Translation

Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
16.4K
RNA Editing02:23

RNA Editing

RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
9.3K
Comparing Copy Number Variations and SNPs02:26

Comparing Copy Number Variations and SNPs

Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
18.1K
RNA Stability01:53

RNA Stability

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
34.2K