Related Experiment Video

Updated: Jul 6, 2026

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
10:06

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

Separable roles for rent1/hUpf1 in altered splicing and decay of nonsense transcripts

Joshua T Mendell1, Colette M J ap Rhys, Harry C Dietz

  • 1Institute of Genetic Medicine and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 858 Ross Building, 720 Rutland Avenue, Baltimore, MD 21205, USA.

Science (New York, N.Y.)
|September 14, 2002
PubMed

Insights

Nonsense-mediated mRNA decay (NMD) factors influence pre-mRNA processing. The study found that rent1/hUpf1, essential for NMD, also impacts nonsense-mediated altered splicing (NAS), but NAS is not solely a consequence of NMD.

Area of Science:

  • Molecular Biology
  • Genetics
  • RNA Biology

Background:

  • The impact of reading frame disruption on pre-messenger RNA (pre-mRNA) processing remains unclear.
  • Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that degrades aberrant mRNAs containing premature stop codons.
  • Nonsense-mediated altered splicing (NAS) is a related phenomenon where premature stop codons can influence splicing outcomes.

Purpose of the Study:

  • To investigate the role of NMD factors in NAS.
  • To determine if NAS is an indirect consequence of NMD.
  • To elucidate the specific functions of rent1/hUpf1 and rent2/hUpf2 in these processes.

Main Methods:

  • Utilized RNA interference (RNAi) in mammalian cells to inhibit the expression of key NMD factors.
  • Assessed the effects of inhibition on both NMD and NAS of nonsense T cell receptor beta transcripts.
  • Examined the subcellular localization of rent1/hUpf1.

Main Results:

  • Inhibition of rent1/hUpf1 abrogated both NMD and NAS.
  • Inhibition of rent2/hUpf2 stabilized nonsense transcripts but did not disrupt NAS.
  • Demonstrated that NAS and NMD are genetically separable functions of rent1/hUpf1.
  • Showed that rent1/hUpf1 enters the nucleus, suggesting a direct role in early mRNA biogenesis.

Conclusions:

  • NAS relies on a component of the nonsense surveillance machinery (rent1/hUpf1).
  • NAS is not an indirect consequence of NMD.
  • Rent1/hUpf1 has distinct roles in both NMD and NAS, with potential direct involvement in nuclear mRNA processing.

More Related Videos

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins11:34

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins

Published on: August 9, 2019

Identification of Alternative Splicing and Polyadenylation in RNA-seq Data08:35

Identification of Alternative Splicing and Polyadenylation in RNA-seq Data

Published on: June 24, 2021

Related Concept Videos

Mutations01:39

Mutations

Overview
Mutations01:39

Mutations

Overview
Gene Conversion02:08

Gene Conversion

Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Gene Conversion02:08

Gene Conversion

Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
Point and Frameshift Mutations01:30

Point and Frameshift Mutations

Point mutations are genetic alterations involving the change of a single nucleotide base pair in DNA. Depending on how the alteration affects protein synthesis, they can lead to various consequences.Point mutations fall into the following types:Silent mutations occur when a nucleotide change does not alter the amino acid sequence due to the redundancy of the genetic code. For instance, changing ACC to ACA still encodes threonine, leaving the protein function unaffected. This occurs because...