La-related protein 1 Antibodies

La-related protein 1 (LARP1)

RNA-binding protein that promotes translation of certain classes of mRNAs downstream of the mTORC1 complex (PubMed:24532714, PubMed:25940091). Associates with the mRNA 5'cap in an MTOR-dependent manner and associates with mRNAs containing a 5' terminal oligopyrimidine (5'TOP) motif, which is present in mRNAs encoding for ribosomal proteins and lots of components of the translation machinery (PubMed:24532714, PubMed:25940091, PubMed:26206669).

Associates with actively translating ribosomes via interaction with PABPC1/PABP and stimulates translation of mRNAs containing a 5'TOP, thereby regulating cell growth and proliferation (PubMed:20430826, PubMed:25940091). Positively regulates the replication of dengue virus (DENV) (PubMed:26735137).

Gene Information

Human
Gene Name:	LARP1
Uniprot:	Q6PKG0
Entrez:	23367

Family

Belongs to:
LARP family

Alternative Names

KIAA0731LARPMGC19556; La ribonucleoprotein domain family member 1; La ribonucleoprotein domain family, member 1; la-related protein 1

Molecular Weight

Mass (kDA):
123.51 kDA

Genomic Context

Human
Location:	5q33.2
Sequence:	5; NC_000005.10 (154682979..154817605)

Subcellular Localizations

Cytoplasm. Cytoplasmic granule. Colocalizes with RPTOR and PABPC1 in cytoplasmic granules that resemble stress granules.

Diseases

• Malignant Neoplasms
• Neoplasms
• Mammary Neoplasms
• Lung Neoplasms
• Prostatic Neoplasms
• Malignant Neoplasm Of Breast

Interacting Proteins

• CCDC155

Pathways

• Translation
• Transport
• Cell Division
• Vesicle Transport
• Cell Migration
• Cell Proliferation
• Head Involution

• Oogenesis
• Spermatogenesis

PTMs

• Phosphorylation

• Methylation

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/LARP1

Best Uses Of The LARP1 Marker

Recent research demonstrated that LARP1 was upregulated by hepatocellular carcinoma cells. The gene is responsible for repressing TOP mRNA translation by binding to the m 7 GpppG region. This finding is interesting because it indicates that LARP1 may bind to the core of DM15 mRNA. However, the methyl-group points away form this core, and is not clear as to what it does.

Hepatocellular cancer has a higher expression of LARP1

LARP1 can be found on chromosome 5,q33.2. It plays a role in embryogenesis, cell-cycle progression, and fertilization. Researchers have identified its expression in 15 human cell types and 272 HCC samples. They examined paired lesions and adjacent tissue that is not cancerous to determine if there were any correlations between LARP1 expression, clinical characteristics, and survival.

Boster Bio partnered with researchers to develop high affinity antibodies for the detection LARP1 within hepatocellular tumors. These antibodies are highly cited, and have been validated for use in immunohistochemistry, Western Blotting, and ELISA. Boster Bio has high-affinity antibodies that researchers can now access from around the world.

A genetic mutation of LARP1 can increase the chance of developing hepatitis B/C. This inflammatory response promotes hepatocellular carcinoma. The T-to -G transversion in vitro enhances the promoter's activity.

LARP1 binds to m 7 GpppG

Designed to recognize mRNAs with seven-methylguanosine caps, the LARP1 marker can be used to detect mRNAs with this cap. The molecule recognizes both m7G caps and the conserved 5’-terminal C residue. LARP1 is highly specific to mRNAs with a m7GpppC caps. In this case, mRNAs containing the cap mimic the m7GpppC motif.

LARP1 is a competitor to mTORC1 that regulates the translation of TOP-mRNAs. The protein binds to the 5’TOP motif of mRNAs, promoting efficient translation. Its DM15 region is cap-binding and it is the DM15domain that binds the mRNA fragment. LARP1 is a key regulator for the translation mRNAs. This is due to the fact that mTORC1 has to be present in order to ensure efficient translation.

The LARP1 protein binds to the 5' end of the mRNA and prevents eIF4F from assembly. It is therefore a key marker in ribosome formation. The LARP1 gene marker can be used for a variety research projects, including those involving human mitochondrial RNA. The LARP1 marker can be used for screening mRNAs related to eIF4E. It is used in identifying mRNAs containing DM15.

LARP1 represses TOP mRNA translation

It is still unclear the role of LARP1 as a regulator of TOP mRNA translation. A molecular analysis has shown that the C terminus of LARP1 is mTOR-dependently associated with polysomes through PAP. However, the protein appears to have stronger effects on TOP mRNA transcript translation than on general mRNA transcript translation.

The mechanism by which LARP1 represses TOP transcripts is not clear, but it involves mTORC1 in regulating its translation. LARP1 competes against the eIF4F to regulate specific mRNA translations. The molecular interactions between LARP1 with the m7Gpppp cap proteins and adjacent 5'TOP motif indicate a role of LARP1 in this process. In order to inhibit TOP mRNA translation, LARP1 dispenses eIF4E and blocks association with eIF4G1.

Because the R840 motif mediates the association between RAPTOR and LARP1, it is likely that this conserved molecular motif explains the low affinity to the mTORC1 mTORC1 protein. However, R840 in LARP1 has a charge-reversed R840 which decreases RAPTOR binding affinity. RAPTOR binding in LARP1 did not change when T779 was replaced with alanine. LARP2 (and LARP3) do not interact with one another. Therefore, further research will be needed in order to discover the molecular mechanism LARP1 uses to suppress TOP mRNA translation.

LARP1 methyl region points away from the core DM15 region

LARP1 regulates the stability of ribosomal proteins and translation factors and interacts with the 5'TOP mRNA. However, until now, the RNA interaction site of LARP1 has remained elusive. The crystal structure of LARP1 now reveals a structurally-related RNA binding region that is highly conserved. This domain includes the DM15 boxes. These structural data also provide insight into how these RNA-binding regions function. Moreover, this crystal structure provides insights into the mechanism by which LARP1 regulates mTOR.

The DM15 region of human LARP1 is predicted to contain two evolutionarily conserved amino acid sequences. The DM15 region has three to four alpha helices. They are offset by forty degrees. These helices also contain concave and a Cterminal Helix. LARP1 actually has pseudo-twofoldsymmetry. The two DM15 modules are separated by a short gap.

Molecular modeling has shown that the LARP1 methyl groups are located far from the core of DM15. Electrostatic profile calculations of the DM15 surface have revealed two positively charged patches, which are present in ninety percent of LARP1 proteins. These amino acids are located on the concave side DM15 region, which is often the site for intermolecular interactions. These conserved amino acids are found in the DM15 region. Biochemical analysis confirms that they bind RNA. However, mutations Y883A or R840E obstruct LARP1's ability RNA binding.

LARP1 binds with m 7 GpppC motif

The LARP1 gene is a 5’TOP motif-binding proteins. It plays a fundamental role in recognizing and binding to the m7 GpppC motif that is unique to TOP mRNAs. TOP mRNAs are the only ones that encode all of core proteins in the ribosomes and translation apparatus. LARP1 may regulate translation and stability of this subclass mRNAs.

The DM15 region within LARP1 makes it unique among cap-binding protein. This region stabilizes the nucleobase of m 7 GTP between two conserved aromatic amino acids. This region may interact with other regions in the LARP1 protein through a 5’-5’ triphosphate linking. This linkage binds the m7 Gppp component to the first nucleotide cytidine of the TOP motif.

Co-crystallization was used for the determination of the structure. Co-crystallization of DM15 molecule and part of the RPS6 5’TOP motif led to a crystal lattice containing both RNA molecules. One protein molecule binds nucleotides 1-5 of one RNA molecule, while the other binds the 3' guanosine (G8) of an RNA molecule in a neighboring unit cell.

Membrane staining enhances protein transfer efficiency

Boster Bio's improved membrane-staining system allows for rapid protein transfers. The transfer buffer allows membrane to stain proteins, while a gel is placed between them. The sandwich is tightly clamped so that air bubbles cannot form between them. The sandwich is then immersed into a buffer and an electric field. As proteins move towards the positively-charged electrode, the membrane binds them with the gel.

The membrane used is composed of two materials: nitrocellulose or polyvinylidene difluoride. Nitrocellulose membranes produce little or no nonspecific staining. They can also be brittle and can remove small molecular protein during washing. The PVDF membrane has a higher sensitivity, resolution, as well as affinity. The nitrocellulose membrane can also allow for the transfer protein with a high degree uniformity.

The primary antibodies used for this purpose were either goat IgG anti-rabbit IgG. Membrane staining was performed after the primary antibodies were added. After washing with distilled water three times, the samples were counterstained with hematoxylin and differentiated using 0.1% hydrochloric acid. The results were then analysed using image-pro plus 6. The ratio of target and b–actin was calculated to determine the intensity.

Film about Autoradiography

This kit measures a marker of EMT (extracellular matrix reorganization), which has been linked to resistance to targeted chemotherapy therapies. The test is fast and accurate, and compatible to many types of tumors. Currently, there are three approved uses for this marker, each of which has specific characteristics. Here are some examples. Continue reading to learn even more. We've compiled a list highlighting the benefits and disadvantages of the LARP1-test.

The LARP1 gene recognizes the m7G cap as well as the 5-cytidine at the TOP sequence of mRNA. The LARP1 DM15 binding region binds m7GpppC dinucleotide. The m7GpppC motifs is an important distinction among the TOP mRNAs as well as most of the cellular mRNAs. This is because most cellular and cellular mRNAs contain a purine in position +1.

The LaRP1 gene encodes a transcription factor that regulates translation of TOP mRNAs. It binds 5'TOP on the mRNAs. This gene is important for ribosome biogenesis, and mTORC1 is crucial for its efficient translation. Best uses of the LARP1 gene marker include screening of mRNAs and identifying cancer cell lines.