Related Experiment Video

Updated: Jun 17, 2025

Rapid Isolation of the Mitoribosome from HEK Cells
09:33

Rapid Isolation of the Mitoribosome from HEK Cells

Published on: October 4, 2018

11.0K

Structural basis of LRPPRC-SLIRP-dependent translation by the mitoribosome

Vivek Singh1, J Conor Moran2, Yuzuru Itoh3,4

  • 1Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Solna, Sweden.

Nature Structural & Molecular Biology
|August 12, 2024
PubMed

Insights

Leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) acts as an mRNA delivery factor in mitochondria. The LRPPRC-SLIRP complex regulates mitochondrial gene expression by modulating mRNA translation.

Area of Science:

  • Mitochondrial biology
  • Molecular genetics
  • Structural biology

Background:

  • Mitochondrial mRNAs require stabilization for proper function.
  • Leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) is a known factor for mRNA stabilization in mammalian mitochondria.

Purpose of the Study:

  • To characterize LRPPRC as an mRNA delivery factor.
  • To determine the structural basis of LRPPRC-SLIRP complex formation with mRNA and the mitoribosome.
  • To investigate the transcript-specific effects of LRPPRC on mitochondrial mRNA translation.

Main Methods:

  • Cryo-electron microscopy to determine the structure of the LRPPRC-SLIRP-mRNA-mitoribosome complex.
  • RNA sequencing, metabolic labeling, and mitoribosome profiling to assess mRNA translation efficiency.

Main Results:

  • The cryo-EM structure reveals LRPPRC association with mitoribosomal proteins, forming a corridor for mRNA handoff.
  • SRA stem-loop-interacting RNA-binding protein (SLIRP) binds mRNA and stabilizes LRPPRC.
  • LRPPRC influences mitochondrial mRNA translation efficiency in a transcript-specific manner, notably affecting cytochrome c oxidase subunits 1 and 2.

Conclusions:

  • LRPPRC-SLIRP functions as an mRNA delivery factor, recruiting mitochondrial mRNAs to modulate their translation.
  • The LRPPRC-SLIRP complex is a key regulator of the mitochondrial gene expression system.

More Related Videos

De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data08:23

De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data

Published on: February 18, 2022

3.5K
RIBO-seq in Bacteria: a Sample Collection and Library Preparation Protocol for NGS Sequencing12:05

RIBO-seq in Bacteria: a Sample Collection and Library Preparation Protocol for NGS Sequencing

Published on: August 7, 2021

8.2K

Related Concept Videos

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,...
13.2K
Initiation of Translation02:33

Initiation of Translation

Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
32.1K
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...
7.2K
Ribosomes01:27

Ribosomes

Ribosomes translate genetic information encoded by messenger RNA (mRNA) into proteins. Both prokaryotic and eukaryotic cells have ribosomes. Cells that synthesize large quantities of protein—such as secretory cells in the human pancreas—can contain millions of ribosomes.
Ribosome Structure and Assembly
Ribosomes are composed of ribosomal RNA (rRNA) and proteins. In eukaryotes, rRNA is transcribed from genes in the nucleolus—a part of the nucleus that specializes in ribosome...
67.6K
Termination of Translation01:44

Termination of Translation

The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is the site where the peptide bond is formed - and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through...
25.3K
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K