Spliceosome

Spliceosome

Spliceosome ball cycle

The spliceosome is a large and complex molecular machine found primarily within the nucleus of eukaryotic cells. It is responsible for the removal of introns from a transcribed pre-mRNA, a type of primary transcript. This process is known as RNA splicing. The spliceosome is composed of small nuclear RNAs (snRNAs) and a variety of associated protein factors. Together, these components form small nuclear ribonucleoproteins (snRNPs), which are the core units of the spliceosome.

Structure

The spliceosome is a dynamic assembly of five snRNPs, known as U1, U2, U4, U5, and U6, along with numerous associated proteins. Each snRNP contains a specific snRNA and a set of proteins. The snRNAs are crucial for recognizing the splice sites on the pre-mRNA and for catalyzing the splicing reactions.

Yeast tri-snRNP

The spliceosome undergoes a series of conformational changes during the splicing cycle. Initially, the U1 snRNP binds to the 5' splice site, and the U2 snRNP binds to the branch point sequence. The U4/U6.U5 tri-snRNP complex then joins the assembly, bringing the splice sites into close proximity. The U1 and U4 snRNPs are released, and the spliceosome undergoes further rearrangements to form the active site for catalysis.

Function

The primary function of the spliceosome is to remove introns from pre-mRNA transcripts. This process involves two transesterification reactions. In the first step, the 2'-hydroxyl group of the branch point adenosine attacks the 5' splice site, forming a lariat structure. In the second step, the 3'-hydroxyl group of the upstream exon attacks the 3' splice site, resulting in the ligation of the exons and the release of the intron lariat.

The precise removal of introns and the joining of exons are crucial for the generation of mature mRNA molecules that can be translated into functional proteins. Errors in splicing can lead to the production of aberrant proteins and are associated with various diseases.

Spliceosome Assembly and Dynamics

The assembly of the spliceosome is a highly regulated and dynamic process. It begins with the recognition of the 5' splice site by the U1 snRNP and the branch point by the U2 snRNP. The subsequent recruitment of the U4/U6.U5 tri-snRNP complex is a critical step in forming the spliceosome.

The spliceosome undergoes several rearrangements to become catalytically active. These rearrangements involve the release of the U1 and U4 snRNPs and the formation of the active site by the U2, U5, and U6 snRNPs. The dynamic nature of the spliceosome allows it to accurately and efficiently process a wide variety of pre-mRNA substrates.

Related Pages

• RNA splicing
• Small nuclear RNA
• Ribonucleoprotein
• Eukaryotic cell
• Intron
• Exon