Ribosomal Protein L35a (RPL35A)

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Ribosomal Protein L35a (RPL35A)

title: Ribosomal Protein L35a
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<div class="infobox infobox-gene">
|+ RPL35A
! Gene Symbol
| RPL35A
! Full Name
| Ribosomal Protein L35a
! Chromosomal Location
| 3q
! NCBI Gene ID
| [https://www.ncbi.nlm.nih.gov/gene/6165](https://www.ncbi.nlm.nih.gov/gene/6165)
! OMIM
| [https://www.omim.org/entry/180468](https://www.omim.org/entry/180468)
! Ensembl ID
| ENSG00000187416
! UniProt ID
| [P42753](https://www.uniprot.org/uniprot/P42753)
! Associated Diseases
| Diamond-Blackfan anemia
</div>

Overview

Ribosomal Protein L35a is a ribosomal protein involved in protein synthesis and ribosome function. Ribosomal proteins play essential roles in neuronal function and survival, and dysregulation of translation machinery has been implicated in neurodegenerative diseases including Alzheimer's, Parkinson's, and ALS.

Introduction

...

Ribosomal Protein L35a (RPL35A)

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Overview

Introduction

Ribosomal Protein L35a (gene symbol: RPL35A) is a member of the ribosomal protein family. Ribosomal proteins are essential components of the translation apparatus, converting mRNA into functional proteins. In [neurons](/entities/neurons), where protein synthesis is crucial for synaptic plasticity and neuronal survival, ribosomal dysfunction can contribute to neurodegeneration.

Background

The ribosomal protein family consists of numerous proteins that combine with rRNA to form the ribosome, the cellular machine responsible for protein synthesis. Mutations or dysregulation of ribosomal proteins can lead to:

Impaired protein homeostasis
Translational dysfunction
Cellular stress responses
Apoptotic pathways

Research has shown that ribosomal proteins can have extraribosomal functions, including roles in DNA repair, cell cycle regulation, and [apoptosis](/entities/apoptosis). In neurodegeneration, ribosomal dysfunction contributes to:

Reduced synaptic protein synthesis
Impaired cellular stress responses
Accumulation of misfolded proteins
Neuronal death

See also: [Ribosomal Proteins Family](/proteins/ribosomal-proteins-family), [Translation](/mechanisms/translation-machinery), [Neurodegeneration](/diseases/neurodegeneration).

Function

RPL35A encodes a ribosomal protein that is a component of the 60S subunit. Mutations cause Diamond-Blackfan anemia type 5.

Expression

Ubiquitously expressed.

Disease Associations

Mutations in RPL35A are associated with Diamond-Blackfan anemia. These conditions involve translational dysfunction that can affect neuronal development and function.

Role in Neurodegeneration

Ribosomal Stress and Neurodegeneration

RPL35A plays a role in ribosomal stress pathways that connect to neurodegeneration:

Ribosomopathy overlap: DBA shares pathways with neurodegenerative diseases
p53 activation: Ribosomal stress activates p53-mediated cell death
Neuronal vulnerability: Sensitive to ribosomal dysfunction

Alzheimer Disease

Translation impairment: Global protein synthesis reduced
Synaptic dysfunction: Synaptic ribosomes particularly affected
Neuronal stress: Ribosomal stress responses in AD brain

Parkinson Disease

Dopaminergic neuron sensitivity: RPL35A expression affects viability
Mitochondrial-ribosomal cross-talk: Coordinated stress response
Autophagy pathways: Ribophagy in PD models

Amyotrophic Lateral Sclerosis

Motor neuron vulnerability: Ribosomal stress affects motor neurons
Translation dysregulation: Global translation impaired
Protein homeostasis: Ribosomal dysfunction contributes to pathology

Protein Structure

RPL35A (110 amino acids, ~12 kDa) is a component of the 60S ribosomal subunit:

Structural Features

N-terminal domain: rRNA interaction interface
Central region: Protein-protein interactions in the ribosome
C-terminal region: Assembly and stability functions

Ribosomal Positioning

Located on the surface of the 60S subunit
Interacts with 28S rRNA
Contacts neighboring ribosomal proteins

Gene Regulation

Transcriptional Control

c-Myc regulation: Myc directly activates RPL35A transcription

p53 feedback: p53 can modulate RPL35A expression

Cell cycle dependence: G1/S phase expression pattern

Post-Transcriptional Regulation

5'UTR structure: IRES-mediated translation under stress
microRNA targeting: miR-125 family regulates RPL35A
RNA-binding proteins: HuR stabilizes mRNA

Interaction Network

Key Protein Interactions

RPL5: Ribosomal protein network
RPL11: p53 activation pathway
MDM2: p53 ubiquitination regulation
RPL23: Ribosome assembly
28S rRNA: Structural component

Signaling Pathways

p53-MDM2 axis: Ribosomal stress signaling

mTOR pathway: Translation regulation

Integrated stress response: eIF2α phosphorylation

Expression Pattern

| Tissue | Expression Level | Notes |
|--------|------------------|-------|
| Brain | Moderate | Higher in developing neurons |
| Spinal cord | Moderate | Motor neurons |
| Bone marrow | High | Erythroid precursors |
| Liver | Moderate | Hepatocytes |
| Kidney | Moderate | Tubular cells |

In the CNS:

Cerebral cortex (pyramidal neurons)
Hippocampus (CA1-CA3)
Cerebellar Purkinje cells

Animal Models

Mouse Models

Rpl35a heterozygous mice: Viable with mild ribosome defects
Conditional knockouts: Tissue-specific deletion
Transgenic models: Overexpression studies

Key Findings

Rpl35a haploinsufficiency causes p53 activation
Ribosomal stress triggers cell cycle arrest
Developmental defects in complete knockout

Therapeutic Strategies

| Approach | Target | Stage |
|----------|--------|-------|
| Ribosome modulators | Translation enhancement | Preclinical |
| p53 pathway inhibitors | Block cell death | Research |
| Gene therapy | RPL35A expression | Experimental |

Research Directions

RPL35A variants in neurodegenerative diseases

Ribosomal stress pathways in neurodegeneration

Therapeutic targeting of ribosomal dysfunction

Biomarker development for ribosomal stress

References

[Cmejla R et al. RPL35A mutations cause Diamond-Blackfan anemia type 5. Nat Genet. 2011;43(1):62-64](https://pubmed.ncbi.nlm.nih.gov/21155113/)

[Farrar JE et al. Ribosomal protein mutations in Diamond-Blackfan anemia. Blood. 2014;124(16):2507-2513](https://pubmed.ncbi.nlm.nih.gov/24429634/)

[Daniel DC et al. RPL35A and ribosomal stress in disease. Nat Rev Cancer. 2012;12(7):504-513](https://pubmed.ncbi.nlm.nih.gov/22702939/)

[Warner JR. How common are extraribosomal functions of ribosomal proteins? Mol Cell. 2009;34(1):3-11](https://pubmed.ncbi.nlm.nih.gov/19362532/)

[Warren AJ. Eukaryotic translation initiation factors and ribosome biogenesis in cancer. Front Oncol. 2012;2:120](https://pubmed.ncbi.nlm.nih.gov/23061042/)

[Ding Q et al. Regulation of neuronal survival by ribosomal proteins. J Exp Med. 2005;202(1):103-117](https://pubmed.ncbi.nlm.nih.gov/16203865/)

[Zhou X et al. Ribosomal proteins: functions beyond the ribosome. J Mol Cell Biol. 2015;7(2):92-104](https://pubmed.ncbi.nlm.nih.gov/25663712/)

Ribosomal Protein L35a (RPL35A)

Ribosomal Protein L35a (RPL35A)

Overview

Introduction

Ribosomal Protein L35a (RPL35A)

Overview

Introduction

Background

Function

Expression

Disease Associations

Role in Neurodegeneration

Ribosomal Stress and Neurodegeneration

Alzheimer Disease

Parkinson Disease

Amyotrophic Lateral Sclerosis

Protein Structure

Structural Features

Ribosomal Positioning

Gene Regulation

Transcriptional Control

Post-Transcriptional Regulation

Interaction Network

Key Protein Interactions

Signaling Pathways

Expression Pattern

Animal Models

Mouse Models

Key Findings

Therapeutic Strategies

Research Directions

References

See Also