Related Experiment Video

Updated: Mar 25, 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

9.5K

Long noncoding RNA Saf and splicing factor 45 increase soluble Fas and resistance to apoptosis

Olga Villamizar1,2, Christopher B Chambers1, Janice M Riberdy3

  • 1Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, Illinois, USA.

Oncotarget
|February 18, 2016
PubMed

Insights

A novel long non-coding RNA, Saf, interacts with splicing factor SPF45 to regulate Fas receptor alternative splicing. This mechanism produces soluble Fas (sFas) protein, protecting cancer cells from apoptosis and promoting tumor survival.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Programmed cell death (apoptosis) is crucial for multicellular organisms.
  • Fas receptor (Fas)-Fas ligand (FasL) interaction mediates a key apoptotic pathway.
  • Cancer cells often resist Fas-mediated apoptosis by downregulating Fas or producing soluble Fas (sFas).

Purpose of the Study:

  • To elucidate the mechanism by which the long non-coding RNA (lncRNA) Saf modulates Fas receptor alternative splicing.
  • To identify the protein partners involved in Saf-mediated alternative splicing.
  • To understand how this mechanism contributes to cancer cell survival.

Main Methods:

  • Nuclear localization studies of Saf.
  • RNA immunoprecipitation to detect Saf-Fas pre-mRNA interactions.
  • Co-immunoprecipitation to identify protein interactions with Saf.
  • Analysis of alternative splicing products and apoptosis assays.

Main Results:

  • Saf is localized in the nucleus and interacts with Fas pre-mRNA.
  • Saf interacts with the human splicing factor 45 (SPF45).
  • This interaction facilitates alternative splicing of Fas pre-mRNA, leading to exon 6 exclusion and production of sFas.
  • The resulting sFas protein protects cells from FasL-induced apoptosis.

Conclusions:

  • A novel mechanism involving the lncRNA Saf and SPF45 regulates Fas receptor alternative splicing.
  • This pathway generates sFas, conferring resistance to apoptosis in neoplastic cells.
  • This discovery offers new insights into cancer cell survival strategies and potential therapeutic targets.
Keywords:
FasSafalternative splicingapoptosislong-noncoding RNA

More Related Videos

A Reporter Based Cellular Assay for Monitoring Splicing Efficiency08:53

A Reporter Based Cellular Assay for Monitoring Splicing Efficiency

Published on: September 15, 2021

3.3K
Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells07:23

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells

Published on: May 30, 2025

1.3K

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...
61.3K
RNA Splicing01:32

RNA Splicing

20.1K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
9.2K
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...
26.2K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.4K
siRNA - Small Interfering RNAs02:30

siRNA - Small Interfering RNAs

Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
19.0K