A 6-month-old boy is evaluated in the clinic due to delayed motor development. The mother reports that the boy is weaker than other children his age. He can barely lift his head up when prone and is unable to roll to the side. Physical examination shows generalized hypotonia and decreased deep tendon reflexes. Further evaluation reveals mutation of a protein involved in the assembly of small nuclear ribonucleoproteins (snRNPs) in motor neurons. This patient most likely has impaired function of which of the following cellular elements?

Question

A 6-month-old boy is evaluated in the clinic due to delayed motor development.  The mother reports that the boy is weaker than other children his age.  He can barely lift his head up when prone and is unable to roll to the side.  Physical examination shows generalized hypotonia and decreased deep tendon reflexes.  Further evaluation reveals mutation of a protein involved in the assembly of small nuclear ribonucleoproteins (snRNPs) in motor neurons.  This patient most likely has impaired function of which of the following cellular elements?

Quizplus · Accepted Answer

11ec160b_36f1_0837_9249_3bf7b60eccdf_MD0001_00 This infant with delayed motor development and flaccid paralysis (eg, hypotonia, decreased deep tendon reflexes) likely has spinal muscular atrophy. This condition is caused by mutations in the survival motor neuron (SMN1) gene, which encodes a protein involved in assembly of small nuclear ribonucleoproteins (snRNPs) in lower motor neurons. Defective snRNP assembly results in impaired spliceosome function and degeneration of anterior horn cells in the spinal cord. RNA molecules that carry out functions without first being translated into proteins are called non-coding RNAs. These include small nuclear RNA (snRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA). snRNA is transcribed by RNA polymerase II and associates with specific proteins to form snRNPs. A collection of snRNPs and other proteins on pre-mRNA is referred to as a spliceosome. Spliceosomes remove introns from pre-mRNA by cleaving the 5' end of intron 1 (splice donor site) and joining that end to the branch point. The freed 3'-OH of exon 1 then forms a phosphodiester bond with the 5'-phosphate at the splice acceptor site, joining exons 1 and 2. (Choice A) Eukaryotic chromatin is composed of repeated subunits called nucleosomes, which consist of double-stranded DNA wrapped around histone protein cores. Nucleosomes are important for the compact packaging of DNA into chromosomes with the aid of other packaging proteins. (Choice B) Peroxisomes are cytoplasmic organelles containing oxidative enzymes (eg, catalase, D-amino acid oxidase, uric acid oxidase). These organelles are ubiquitous among eukaryotes and are most abundant in the liver and kidneys, where detoxification of ingested and environmental materials occurs. In the liver, peroxisomes also play a role in the breakdown of fatty acids. (Choice C) Proteasomes and lysosomes are responsible for protein/polypeptide degradation. Proteasomes mainly degrade intracellular proteins, whereas lysosomes degrade extracellular proteins and worn-out organelles. (Choice D) Ribosomes are present in the cytoplasm and are required for translation of mRNA into protein. Individual ribosomes are comprised of rRNA and ribosomal proteins. Within the cell, rRNA engages mRNA and facilitates tRNA entry during the formation of polypeptide chains. Educational objective: Small nuclear ribonucleoproteins (snRNPs) are important components of the spliceosome, a molecule which removes introns from pre-mRNA during processing within the nucleus. Spinal muscular atrophy is a disorder caused by mutations in the SMN1 gene, resulting in impaired assembly of snRNPs in lower motor neurons. Infants often have flaccid paralysis due to degeneration of anterior horn cells in the spinal cord. __________ References: Spliceosome structure and function. (http://www.ncbi.nlm.nih.gov/pubmed/21441581) Spinal muscular atrophy: a timely review. (http://www.ncbi.nlm.nih.gov/pubmed/21482919)

A 6-Month-Old Boy Is Evaluated in the Clinic Due to Delayed