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splicing

BiochemistryGene expressionRNA processing

Summary

Splicing is the removal of introns from eukaryotic pre-mRNA and the joining of the remaining exons into mature mRNA, done in the nucleus by the spliceosome. Most testable: alternative splicing lets one gene make several different proteins.

Detail

Meaning: A eukaryotic gene is first transcribed into pre-mRNA containing exons (sequences that stay in the mRNA and are usually translated) and introns (intervening sequences that are removed). The spliceosome, built from snRNPs (small nuclear RNAs bound to proteins), recognizes sequences at the 5′ splice site, the branch point and the 3′ splice site. It cuts out the intron as a lariat and ligates the neighboring exons. This happens in the nucleus along with 5′ capping and addition of the 3′ poly-A tail. Alternative splicing joins different combinations of exons, so one gene can give several mRNAs and protein isoforms.

On the MCAT: Passages often describe a mutation at a splice site. The likely result is exon skipping or intron retention, which changes the protein and can shift the reading frame. Another common setup compares genomic DNA with cDNA, which is made from mature mRNA by reverse transcriptase. The cDNA is shorter because it has no introns. You may also be asked why a tissue-specific protein isoform appears on a gel or blot even though every cell has the same DNA.

Common confusion: Splicing changes the RNA, not the DNA, and alternative splicing is not a mutation. Introns are removed and exons are kept (exons are expressed). Splicing is also separate from capping and tailing, which add to the ends of the transcript instead of removing internal pieces. Bacterial mRNA is generally not spliced.

Sources

  • Lehninger Principles of Biochemistry
  • Molecular Biology of the Cell
  • Biochemistry (Berg, Tymoczko, Stryer)

Written for the MCAT and checked before it was published. For study reference only. Spotted an error? Let us know.

splicing: MCAT Glossary