Expression of alternatively and aberrantly spliced transcripts of the MDM2 mRNA is not tumor-specific

F Bartel1, D Pinkert, W Fiedler

  • 1Institute of Pathology, Faculty of Medicine, University of Halle-Wittenberg, D-06097 Halle/Saale, Germany. frank.bartel@medizin.uni-halle.de

Insights

Shorter MDM2 transcripts, often found altered in cancer, are widely expressed in normal tissues. These variants may have a normal physiological role, not just a role in tumorigenesis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The MDM2 proto-oncogene encodes a protein that inactivates the tumor suppressor p53.
  • Aberrantly spliced MDM2 mRNA transcripts are reported in various human cancers.
  • Some MDM2 isoforms possess transforming abilities, suggesting a role in tumorigenesis.

Purpose of the Study:

  • To investigate the expression and potential function of shorter MDM2 transcripts.
  • To determine if MDM2 transcript alterations are specific to cancer or also occur in normal tissues.
  • To clarify the role of MDM2 transcript variants in cancer development and normal physiology.

Main Methods:

  • Analysis of MDM2 mRNA transcripts in normal and cancerous human tissues.
  • Detection and characterization of alternatively and aberrantly spliced MDM2 variants.
  • Comparison of MDM2 transcript expression patterns between normal tissues and various cancers.

Main Results:

  • Shorter MDM2 transcripts are widely expressed in normal tissues, including lung, renal tissue, and lymphocytes.
  • Alterations in MDM2 RNA transcripts were detected in the majority of analyzed samples.
  • The widespread expression suggests a potential normal physiological function for these variants.

Conclusions:

  • The commonly observed MDM2 transcript variants may possess a normal physiological function.
  • Alterations in MDM2 transcripts are not exclusive to cancer and occur in normal tissues.
  • The role of MDM2 transcript variants in tumorigenesis requires further investigation in light of their normal expression patterns.

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
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...
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...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...