Zfrp8/PDCD2 Interacts with RpS2 Connecting Ribosome Maturation and Gene-Specific Translation

Svetlana Minakhina1, Tatyana Naryshkina1, Neha Changela1

  • 1Waksman Institute, Rutgers, The State University of New Jersey, Piscataway, New Jersey, United States of America.

Plos One
|January 26, 2016
PubMed

Insights

Zfrp8/PDCD2 protein is crucial for stem cell maintenance and cancer cell proliferation. This study reveals its role in regulating mRNA-ribonucleoprotein complexes and ribosome assembly, impacting cytoplasmic localization and translation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Zfrp8/PDCD2 is a conserved protein vital for stem cell maintenance in flies and mammals.
  • It is also essential for rapidly proliferating cells, including cancer cells.
  • Previous research indicated Zfrp8's involvement in mRNA ribonucleoprotein (mRNP) complex formation and Transposable Element (TE) RNA control.

Purpose of the Study:

  • To investigate the function of Zfrp8/PDCD2 in regulating RNA metabolism and ribosome biogenesis.
  • To elucidate the molecular mechanisms by which Zfrp8/PDCD2 controls mRNA and TE transcript localization.
  • To determine Zfrp8/PDCD2's interaction with ribosomal components and its role in ribosome assembly.

Main Methods:

  • Utilized Zfrp8/PDCD2 knockdown (KD) in ovaries to observe effects on mRNA and TE transcript localization.
  • Investigated the interaction between Zfrp8/PDCD2 and the 40S small ribosomal subunit component, RpS2 (uS5).
  • Employed fluorescently tagged ribosomal proteins to study their distribution in cells with and without Zfrp8/PDCD2.

Main Results:

  • Knockdown of Zfrp8/PDCD2 led to increased nuclear accumulation of specific mRNAs and TE transcripts.
  • Demonstrated a direct interaction between Zfrp8/PDCD2 and the RpS2 protein of the 40S ribosomal subunit.
  • Showed that Zfrp8/PDCD2 regulates cytoplasmic levels of 40S ribosomal subunit components, but not their nuclear/nucleolar localization.

Conclusions:

  • Zfrp8/PDCD2 plays a role in late stages of ribosome assembly.
  • The protein likely controls the binding of specific mRNA-ribonucleoprotein complexes to the small ribosomal subunit.
  • This regulation ultimately influences the cytoplasmic localization and translation of these transcripts.

Related Concept Videos

Directing Proteins to the Rough Endoplasmic Reticulum01:34

Directing Proteins to the Rough Endoplasmic Reticulum

The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
18.3K
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,...
15.1K
Ribosomal RNA Synthesis02:53

Ribosomal RNA Synthesis

4.8K
Translational Regulation01:29

Translational Regulation

Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
802
Regulated mRNA Transport02:22

Regulated mRNA Transport

In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
7.2K
Riboswitches01:56

Riboswitches

Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
10.1K