Ribonucleoproteins (RNPs) are cellular components found across all forms of life. These complexes are made of RNA (ribonucleic acid) and proteins. Functioning as molecular machines, RNPs are widespread throughout cells and play a role in numerous biological processes, performing diverse tasks that contribute to cellular operation and health.
What Are Ribonucleoproteins?
Ribonucleoproteins are complexes formed when RNA molecules associate with specific RNA-binding proteins (RBPs). The RNA component can be various types, including messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), and microRNA (miRNA). These RNA types contribute unique structural and functional properties to the RNP complex.
Proteins in RNPs interact with RNA through various structural motifs, including aromatic amino acid residues and positively charged lysine residues that stabilize interactions. This combination of RNA and protein allows for the assembly of highly organized structures. For example, the ribosome is a large RNP that functions in protein synthesis. Over 2,000 different RNPs have been identified, highlighting their widespread presence and diverse forms.
Essential Roles in Cell Function
RNPs perform a wide array of functions within cells, many centered on the flow of genetic information. They are involved in regulating gene expression, ensuring genes are turned on or off at appropriate times and in correct amounts.
Gene Expression Regulation
RNPs play a role in gene expression regulation, particularly in processes like splicing, translation, and mRNA stability and transport. Spliceosomes, for instance, are large RNPs that remove non-coding regions (introns) from messenger RNA (mRNA) precursors. This process, called splicing, ensures that only coding sequences (exons) are joined to form mature mRNA for protein translation.
Ribosomes, large RNPs themselves, are the cellular machinery for protein synthesis (translation). They move along mRNA molecules, reading the genetic code and facilitating amino acid assembly into polypeptide chains. Transfer RNA (tRNA) molecules, also RNPs, act as adapters, bringing correct amino acids to the ribosome based on the mRNA sequence.
Beyond synthesis, RNPs regulate mRNA stability and transport within the cell. They influence how long an mRNA molecule lasts and where it is localized before translation. For example, in neurons, RNPs transport and store mRNA in dendrites for connection formation and strengthening.
Genome Maintenance
RNPs also contribute to genome maintenance. Telomerase, a ribonucleoprotein polymerase, is an example. This enzyme maintains chromosome ends (telomeres) by adding repetitive DNA sequences (TTAGGG). This action counteracts telomere shortening during cell division, protecting genetic information and ensuring genomic stability. Telomerase activity is generally repressed in adult somatic cells but remains active in germ cells and stem cells.
RNA Modification
Some RNPs guide chemical modifications of other RNA molecules. Small nucleolar RNPs (snoRNPs) and small Cajal body RNPs (scaRNPs) are examples. These RNPs guide enzymes to specific sites on ribosomal RNA (rRNA) and small nuclear RNA (snRNA) for modifications like ribose-2′-O-methylation and pseudouridylation. These modifications influence the folding, stability, and function of the modified RNA molecules, impacting processes like ribosome biogenesis.
Other Regulatory Roles
MicroRNAs (miRNAs) are small, non-coding RNA molecules that form microRNP complexes (miRNPs) or RNA-induced silencing complexes (RISC). These complexes are involved in gene silencing by binding to complementary sequences on messenger RNA (mRNA) molecules. Depending on complementarity, miRNPs can destabilize mRNA by shortening its poly(A) tail, lead to its direct cleavage, or reduce its translation. This mechanism allows miRNAs to regulate the expression of up to 90% of genes in humans.
Ribonucleoproteins and Human Health
Dysfunction in ribonucleoproteins can have consequences for human health, contributing to a range of diseases. Errors in RNP formation, function, or regulation can disrupt normal cellular processes.
Neurodegenerative Diseases
RNPs are implicated in neurodegenerative conditions such as Amyotrophic Lateral Sclerosis (ALS), spinal muscular atrophy (SMA), and Huntington’s disease. For example, mutations in genes encoding RNA-binding proteins like TDP-43 and FUS are linked to ALS. In these diseases, RNPs can mislocalize or aggregate, forming insoluble clumps within cells that disrupt neuronal function. Spinal muscular atrophy, a juvenile-onset neurodegenerative disorder, is caused by mutations in the SMN1 gene, affecting the survival motor neuron (SMN) protein, an RNP chaperone. This leads to lower motor neuron loss, causing muscle weakness and atrophy.
Cancers
RNPs also play a role in the uncontrolled cell growth seen in cancers. Alterations in RNP activity can lead to changes in mRNA processing, stability, and translation, affecting gene expression involved in cell proliferation and tumor suppression. For instance, aberrant splicing patterns, often influenced by RNPs like heterogeneous nuclear ribonucleoproteins (hnRNPs), can contribute to cancer development. Abnormal regulation of oncogenes and tumor suppressors by RNA-binding proteins has been associated with various cancer types, including tumor metabolism and drug resistance.
Autoimmune Disorders
In some autoimmune disorders, the immune system mistakenly targets its own RNPs. Anti-RNP antibodies, autoantibodies against ribonucleoproteins, are found in patients with connective tissue diseases like mixed connective tissue disease (MCTD), systemic lupus erythematosus (SLE), and Sjögren’s syndrome. High levels of these antibodies can indicate an autoimmune condition where the immune system attacks connective tissues, leading to symptoms such as joint pain, muscle weakness, and skin rashes. Their presence can be a diagnostic marker for these conditions.
Viral Infections
Viruses often exploit or interact with host RNPs to facilitate their replication and survival. Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), an RNA-binding protein, plays a role in the life cycle of many viruses, including RNA and DNA viruses. The levels and localization of hnRNPA1 can be modulated by different viruses, impacting viral replication and pathogenesis. Some viruses, like Sindbis virus and enteroviruses, may enhance replication through interaction with hnRNPA1, while others, such as hepatitis C virus, might see a protective response. Understanding these interactions offers insights for developing new antiviral strategies.