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Research Progress

Unique Features of mRNA Quality Control Pathway Uncovered in Ciliated Protozoa

Apr 26, 2017

Nonsense-mediated mRNA decay (NMD) is an important mRNA quality control pathway that ensures efficient degradation of transcript with premature termination codons (PTC). This pathway is the therapeutic target in many genetic diseases, such as amyotrophic lateral sclerosis (ALS) and cystic fibrosis, etc.

Protozoa consist of many biological and biomedically important free-living and parasitic early-branching eukaryotes. Studies on them have led to numerous scientific breakthroughs, such as discovery of telomere function, catalytic RNAs, etc. However, the components and molecular mechanisms of NMD are largely unknown in protozoa.

Researchers from Dr. MIAO Wei's lab at Institute of Hydrobiology of Chinese Academy of Sciences, made the first attempt to take the advantage of transcriptome sequencing and mass spectrometry-based proteomics to uncover the unique and conserved aspects of NMD pathway in ciliated protozoan Tetrahymena thermophila. The study was published in Nucleic Acids Research.

By characterization of the functions and protein-protein interactions of deeply conserved NMD factors, researchers have revealed the requirement of conserved up-frame shift proteins (Upf1, Upf2 and Upf3) for the Tetrahymena NMD, and ruled out the involvement of exon-junction complex (EJC) in its NMD.

In addition, a novel nuclease that widely conserved in protozoa was found to be an interacting partner of the Tetrahymena Upf1, and its nuclease activity is possibly essential for removal of many PTC-containing transcripts.

The transcriptome-wide analysis of PTC-containing transcripts suggested that the spliceosomal intron located downstream of a termination codon could trigger NMD, which implies that splicing related factors may be required for PTC recognition in Tetrahymena.

The investigation of the NMD pathway in an early-branching eukaryote can contribute to the understanding of the evolution of NMD pathway, meanwhile it can also contribute to applying highly publicized CRISPR/Cas9 technologies todisrupt the gene of interest by inducing nonsense mutations that will be degraded by NMD in T. thermophila, as well as many other biomedically important protozoa.

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