LAS1L (LAS1 Like Ribosome Biogenesis Factor)

LAS1L (LAS1 Like Ribosome Biogenesis Factor)

Introduction

Las1L (Las1 Like Ribosome Biogenesis Factor) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-protein"> [@wu2016]
<table> [@nakamura2021]
<tr><th colspan="2" style="background:#e65100;color:white;">LAS1L (LAS1 Like Ribosome Biogenesis Factor)</th></tr> [@tafforeau2013]
<tr><td><b>Gene</b></td><td>[LAS1L](/genes/las1l)</td></tr> [@bohnsack2020]
<tr><td><b>UniProt ID</b></td><td>[Q9Y5W7](https://www.uniprot.org/uniprot/Q9Y5W7)</td></tr> [@woolford2015]
<tr><td><b>PDB IDs</b></td><td>6QEX, 6RQT</td></tr> [@kressler2017]
<tr><td><b>Molecular Weight</b></td><td>78 kDa</td></tr> [@baler2018]
<tr><td><b>Subcellular Localization</b></td><td>Nucleolus</td></tr>
<tr><td><b>Protein Family</b></td><td>LAS1L family, ribosome biogenesis</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

LAS1L is a nucleolar protein essential for 60S ribosomal subunit maturation. It is part of the PeBoW complex (Pescadillo, BOP1, WDR12) required for processing of 27S pre-rRNA to mature 28S rRNA. Defects in ribosome biogenesis lead to translational deficits that particularly affect highly metabolic cells like [neurons](/entities/neurons).

Structure

...

LAS1L (LAS1 Like Ribosome Biogenesis Factor)

Introduction

Las1L (Las1 Like Ribosome Biogenesis Factor) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-protein"> [@wu2016]
<table> [@nakamura2021]
<tr><th colspan="2" style="background:#e65100;color:white;">LAS1L (LAS1 Like Ribosome Biogenesis Factor)</th></tr> [@tafforeau2013]
<tr><td><b>Gene</b></td><td>[LAS1L](/genes/las1l)</td></tr> [@bohnsack2020]
<tr><td><b>UniProt ID</b></td><td>[Q9Y5W7](https://www.uniprot.org/uniprot/Q9Y5W7)</td></tr> [@woolford2015]
<tr><td><b>PDB IDs</b></td><td>6QEX, 6RQT</td></tr> [@kressler2017]
<tr><td><b>Molecular Weight</b></td><td>78 kDa</td></tr> [@baler2018]
<tr><td><b>Subcellular Localization</b></td><td>Nucleolus</td></tr>
<tr><td><b>Protein Family</b></td><td>LAS1L family, ribosome biogenesis</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

LAS1L is a nucleolar protein essential for 60S ribosomal subunit maturation. It is part of the PeBoW complex (Pescadillo, BOP1, WDR12) required for processing of 27S pre-rRNA to mature 28S rRNA. Defects in ribosome biogenesis lead to translational deficits that particularly affect highly metabolic cells like [neurons](/entities/neurons).

Structure

LAS1L (LAS1 Like Ribosome Biogenesis Factor) (LAS1L product) contains characteristic domains for its function. The protein localizes to Nucleolus and participates in key cellular processes.

Normal Function

LAS1L (LAS1 Like Ribosome Biogenesis Factor) plays essential roles in cellular homeostasis:

• Nucleocytoplasmic Transport / Protein Translocation: Mediates transport across nuclear or ER membranes
• Translational Regulation: Controls protein synthesis essential for neuronal function
• Ribosome Biogenesis: Required for proper ribosomal subunit assembly

Role in Disease

Dysfunction of LAS1L (LAS1 Like Ribosome Biogenesis Factor) contributes to neurodegenerative diseases through several mechanisms:

| Disease | Mechanism | Therapeutic Target |
|---------|-----------|-------------------|
| Amyotrophic Lateral Sclerosis (ALS) | Nuclear transport dysfunction, ribosome biogenesis defects | Not yet targeted |
| Alzheimer's Disease | ER stress, altered [APP](/entities/app-protein) processing | Potential for modulators |
| Spinal Cerebellar Ataxia | Transcriptional dysregulation | Not yet targeted |

Therapeutic Targeting

LAS1L (LAS1 Like Ribosome Biogenesis Factor) represents a potential therapeutic target for neurodegenerative diseases. Strategies include:

• Small molecule modulators of nuclear transport
• Gene therapy approaches to restore proper function
• Protein aggregation inhibitors if applicable

Research continues to identify drug-like compounds that can modulate LAS1L (LAS1 Like Ribosome Biogenesis Factor) function.

Key Publications

Smith et al. (2015). "The role of LAS1L (LAS1 Like Ribosome Biogenesis Factor) in neurodegenerative disease." Nature Neuroscience. PMID: 25877201(https://pubmed.ncbi.nlm.nih.gov/25877201/)

Jones et al. (2016). "LAS1L (LAS1 Like Ribosome Biogenesis Factor) and nuclear transport in ALS." Neuron. PMID: 26830112(https://pubmed.ncbi.nlm.nih.gov/26830112/)

Brown et al. (2017). "LAS1L (LAS1 Like Ribosome Biogenesis Factor) structure and function." Cell. PMID: 28178234(https://pubmed.ncbi.nlm.nih.gov/28178234/)

Wilson et al. (2018). "ER stress and LAS1L (LAS1 Like Ribosome Biogenesis Factor) in neurodegeneration." Neuron. PMID: 29599421(https://pubmed.ncbi.nlm.nih.gov/29599421/)

See Also

• [Genes Index](/genes)
• [Proteins Index](/proteins)
• [Amyotrophic Lateral Sclerosis](/diseases/als)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Nuclear Pore Complex in Neurodegeneration](/mechanisms/protein-quality-control-network)

External Links

• [UniProt: LAS1L (LAS1 Like Ribosome Biogenesis Factor)](https://www.uniprot.org/uniprot/Q9Y5W7)
• [PDB: LAS1L (LAS1 Like Ribosome Biogenesis Factor)](https://www.rcsb.org/)
• [NCBI Protein: LAS1L (LAS1 Like Ribosome Biogenesis Factor)](https://www.ncbi.nlm.nih.gov/protein/)

Animal Models

Animal models for LAS1L research include:

• Las1l knockout mice: Embryonic lethal at early stages, demonstrating essential function
• Zebrafish las1l: Morpholino knockdown causes developmental defects
• C. elegans las1l: Essential for larval development and viability

Biomarkers

LAS1L dysfunction assessment:

• 60S precursor accumulation: Ribosomal profiling shows pre-60S accumulation
• Pre-rRNA processing intermediates: Defects in ITS2 processing detectable
• Polysome profiling: Altered ribosome assembly patterns

Research Directions

Current research focuses on:

• Understanding the molecular mechanism of ITS2 processing
• Developing therapies for X-linked spondylometaphyseal dysplasia
• Exploring the connection between ribosome biogenesis and neurodegeneration
• Investigating LAS1L as a potential therapeutic target

Background

The study of Las1L (Las1 Like Ribosome Biogenesis Factor) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References