Posttranscriptional regulation of PTEN dosage by noncoding RNAs

Lin He1

  • 1Division of Cellular and Developmental Biology, Molecular and Cellular Biology Department, University of California at Berkeley, Berkeley, CA 94705, USA. lhe@berkeley.edu

Science Signaling
|November 4, 2010
PubMed

Insights

Tumor suppressor gene inactivation is complex. PTEN dosage, regulated by noncoding RNAs like miRNAs, is crucial for tumor development, offering new insights into cancer mechanisms.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The traditional "two-hit" model suggests complete tumor-suppressor gene loss for tumorigenesis.
  • Tumor-suppressor deregulation is complex and varies by cancer type, stage, and other factors.
  • Emerging evidence highlights the critical role of PTEN (phosphatase and tensin homolog) gene dosage in tumor development.

Purpose of the Study:

  • To explore the role of PTEN dosage in tumorigenesis.
  • To investigate how noncoding RNAs regulate PTEN abundance.
  • To understand the molecular mechanisms of dosage-dependent effects in cancer.

Main Methods:

  • Review of existing studies on tumor-suppressor genes, PTEN, and noncoding RNAs.
  • Analysis of posttranscriptional regulation mechanisms.
  • Exploration of PTEN-targeting noncoding RNAs, including microRNAs (miRNAs) and pseudogenes.

Main Results:

  • PTEN dosage is functionally important in tumor development.
  • Noncoding RNAs, such as miRNAs and pseudogenes, are key regulators of PTEN abundance.
  • These PTEN-targeting noncoding RNAs play essential roles in tumor progression.

Conclusions:

  • Tumorigenesis is not solely dependent on complete loss of tumor-suppressor function.
  • PTEN dosage regulation by noncoding RNAs provides a paradigm for understanding oncogene and tumor-suppressor dosage effects.
  • Further research into these mechanisms can reveal new therapeutic targets.

Related Concept Videos

Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
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 (lncRNA)...
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 (lncRNA)...
What is Gene Expression?01:36

What is Gene Expression?

A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised  of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then processed and...
What is Gene Expression?01:42

What is Gene Expression?

Overview
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...