Related Experiment Video
Updated: Jul 18, 2026
11:32
Analysis of mRNA Nuclear Export Kinetics in Mammalian Cells by Microinjection
Published on: December 4, 2010
Nuclear export modulates the cytoplasmic Sir2 homologue Hst2
Jeanne M Wilson1, Viet Q Le, Collin Zimmerman
1Division of Biological Sciences, Section of Molecular Biology, University of California, San Diego, 9500 Gilman Drive, 0347, La Jolla, California 92093, USA.
EMBO Reports
|November 18, 2006
Summary
The yeast Hst2 protein, a Sir2 family member, is actively exported from the nucleus, inhibiting its role as a transcriptional repressor. This nuclear exclusion mechanism is conserved in vertebrate SIRT2 proteins.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Transcription factors regulate gene expression programs.
- The Sir2 family of NAD-dependent deacetylases, including Hst2 and SIRT2, impacts transcription.
- Despite appearing cytoplasmic, Hst2 and SIRT2 are linked to transcriptional regulation.
Purpose of the Study:
- To investigate the subcellular localization and transcriptional regulatory role of yeast Hst2.
- To elucidate the mechanism of Hst2's nuclear exclusion.
- To determine if Hst2's nuclear exclusion impacts its function as a transcriptional repressor.
Main Methods:
- Tracking Hst2 localization between nucleus and cytoplasm.
- Identifying the nuclear export pathway mediated by chromosomal region maintenance 1 (Crm1).
- Analyzing the effect of disrupting Hst2 export on its transcriptional repressor activity.
Main Results:
- Hst2 is predominantly cytoplasmic due to efficient nuclear export.
- Nuclear export of Hst2 is mediated by Crm1 and a leucine-rich nuclear export sequence.
- Inhibiting Hst2 nuclear export enhances its activity as a transcriptional repressor.
- Putative nuclear export sequences were identified in vertebrate SIRT2 proteins.
Conclusions:
- Hst2's nuclear exclusion actively inhibits its function as a transcriptional repressor.
- Active nuclear export is a conserved mechanism for regulating Sir2 homologues, including vertebrate SIRT2.
Related Concept Videos
01:42Nuclear Export
The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
01:34Nuclear Protein Sorting
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
01:45Regulation 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...
02:31Nuclear Export of mRNA
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
02:31Nuclear Export of mRNA
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
01:42Directionality of Nuclear Transport
Ras-related nuclear protein or Ran is a small G protein that cycles between its GTP and GDP bound states. Ran specific regulators, a Ran GTPase Activating Protein or RanGAP present in the cytosol and a Ran guanine nucleotide exchange factor or RanGEF present inside the nucleus regulate GTP/GDP exchange. A high concentration of GTP inside the cells, in addition to this asymmetric distribution of Ran-specific regulators, leads to a higher RanGTP concentration inside the nucleus. This...