SLC45A3-ELK4 functions as a long non-coding chimeric RNA

Fujun Qin1, Yanmei Zhang2, Jia Liu1

  • 1Department of Pathology, University of Virginia, Charlottesville, VA, 22908, USA.

Cancer Letters
|July 19, 2017
PubMed

Insights

A novel long non-coding chimeric RNA (lnccRNA), SLC45A3-ELK4, drives prostate cancer cell proliferation. This fusion RNA regulates cancer growth through its transcript, not its protein product.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Gene fusions in cancer can create fusion proteins or disrupt gene expression.
  • A newly identified phenomenon involves fusion transcripts acting as long non-coding chimeric RNAs (lnccRNAs).

Purpose of the Study:

  • To investigate the role of the SLC45A3-ELK4 fusion transcript in prostate cancer.
  • To determine whether the SLC45A3-ELK4 fusion RNA functions via its protein product or as a non-coding RNA.

Main Methods:

  • Identification of the SLC45A3-ELK4 fusion RNA in prostate cancer.
  • Silencing of the fusion RNA and wild-type ELK4 to assess effects on cell proliferation.
  • Rescue experiments using exogenous expression of the fusion RNA and a non-translatable mutant.
  • Analysis of CDKN1A and other target gene expression.

Main Results:

  • The SLC45A3-ELK4 fusion RNA, while encoding the same protein as ELK4, is present at low levels.
  • Silencing the fusion RNA, but not ELK4, inhibits prostate cancer cell proliferation.
  • The fusion RNA, acting as a transcript, suppresses CDKN1A and other targets, leading to growth arrest.

Conclusions:

  • The SLC45A3-ELK4 fusion RNA regulates prostate cancer cell proliferation through its non-coding transcript function.
  • This finding reveals a novel mechanism where lncRNA function, not protein production, drives cancer progression.

Related Concept Videos

lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
10.0K
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

3.8K
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...
61.0K
Ribosomal RNA Synthesis02:53

Ribosomal RNA Synthesis

Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
15.0K
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.8K
Non-LTR Retrotransposons03:18

Non-LTR Retrotransposons

As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
13.6K