What is the Difference Between Cis and Trans Splicing

The key difference between cis and trans splicing is that cis splicing is an intramolecular mechanism that removes introns and joins the exons that are within the same RNA transcript, while trans-splicing is an intermolecular mechanism that removes introns or outrons and joins the exons that are not within the same RNA transcript.

RNA splicing is a form of RNA processing before protein synthesis. In this process, a newly made pre-messenger RNA transcript is transformed into a mature messenger RNA. Mature messenger RNA helps to produce a protein molecule. During RNA splicing, the introns (non-coding regions) are removed, and exons (coding regions) are joined together to make mature mRNA. Cis and trans splicing are two types of RNA splicing mechanisms.

CONTENTS

1. Overview and Key Difference
2. What is Cis Splicing
3. What is Trans Splicing
4. Similarities – Cis and Trans Splicing
5. Cis vs Trans Splicing in Tabular Form
6. Summary – Cis vs Trans Splicing

What is Cis Splicing?

Cis splicing is an intramolecular mechanism that removes introns and joins the exons that are within the same RNA transcript. Normal cis splicing processes a single RNA molecule. Cis splicing is the typical splicing process of pre mRNA carried out by spliceosomes. In the intron, a donor site (5’ end of the intron), a branch site (near the 3’ end of the intron) and an acceptor site (3’ end of the intron) are highly essential for splicing. The splice donor site includes an invariant sequence GU at the 5’ end of the intron. The splice acceptor site at the 3’ end of the intron has an invariant AG sequence. Upstream from the AG sequence, there is a region called the pyrimidine region (polypyrimidine tract). Further upstream from the polypyrimidine tract, there is a branch point that includes an adenosine nucleotide. This nucleotide is involved in lariat formation.

The major spliceosomes are U1, U2, U4, U5 and U6. Among them, U1 and U2 are very important. In cis splicing, the U1 binds to the 5’ splice site, and U2 binds to the branch point near the 3’ splice site. U5/U4/U6 binds exons at the 5’ site, with U6 binding to U2. Later, U1 is released. U5 shifts from exon to intron, and U6 binds at the 5’ splice site. Furthermore, U4 is also released. U6/U2 catalyzes transesterification, making the 5’ end of the intron ligate to the A nucleotide on intron. This triggers lariat formation. In the formation of a lariat, U5 binds exon at 3’ splice site, and the 5’ site is cleaved. At the final phase of splicing, U2/U5/U6 remain bound to the lariat, and 3’ site is cleaved. In addition to that, the exons are ligated using ATP hydrolysis in this phase.

What is Trans Splicing?

Trans splicing is an intermolecular mechanism that removes introns or outrons and joins the exons that are not within the same RNA transcript. In trans-splicing, there is no 5’ splice site on the pre mRNA molecule for U1 protein to bind. Instead, capped splice leader (SL) RNA is trans-spliced on to sequence in the outron.

Outron is a region of the pre mRNA between the 5’ cap and the trans splice site.  However, U2 protein binds to the 3’ splice site usually. After removing outron, the splice leader (SL) exon is spliced to the first exon on the pre mRNA. Furthermore, trans-splicing is a mechanism that is observed in certain microorganisms such as protists of Kinetoplastae class to express genes.

What are the Similarities Between Cis and Trans Splicing?

• Cis and trans splicing are two types of RNA splicing mechanisms.
• In both mechanisms, introns are removed.
• Also, in both mechanisms, exons are joined to form mature mRNA.
• Both mechanisms are found in eukaryotes.
• These mechanisms are absent in prokaryotes.

What is the Difference Between Cis and Trans Splicing?

Cis splicing is an intramolecular mechanism that removes introns and joins the exons that are within the same RNA transcript, while trans-splicing is an intermolecular mechanism that removes introns or outrons and joins the exons that are not within the same RNA transcript. So, this is the key difference between cis and trans splicing. Furthermore, in cis splicing, introns are removed to form mature mRNA. On the other hand, in trans splicing introns or outrons are removed to form mature mRNA.

The following infographic lists the differences between cis and trans splicing in tabular form for side by side comparison.

Summary – Cis vs Trans Splicing

RNA splicing is a form of RNA processing before the protein synthesis process. Cis and trans splicing are two types of RNA splicing mechanisms that are found in eukaryotes. Cis splicing is an intramolecular mechanism that removes introns and joins the exons that are within the same RNA transcript, while trans-splicing is an intermolecular mechanism that removes introns or outrons and joins the exons that are not within the same RNA transcript. Thus, this concludes the discussion of the difference between cis and trans splicing.

Reference:

1. “RNA Splicing: Introns, Exons and Spliceosome.” Nature News, Nature Publishing Group.
2. “Trans Splicing.” An Overview | ScienceDirect Topics.

Image Courtesy:

1. “Trans-splicing” Von AB – AB (CC BY-SA 3.0) via Commons Wikimedia
2. “Figura-Trans-splicing” By JMRR-UAM – Own work (CC BY-SA 4.0) via Commons Wikimedia