Alternative polyadenylation (APA) is an RNA processing mechanism that regulates gene expression by generating different ends on RNA transcripts of the same gene. Though it affects more than half of human genes, the significance of APA was poorly understood.

Now a new study by The Wistar Institute describes an important function of APA in allowing certain mRNAs to reach specific sites of protein synthesis and reveals that length, sequence and structural properties can determine the destination (and fate) of mRNAs within the cell.

APA) that modifies the tail end of RNA sequences to generate multiple messenger RNAs from the same gene, which scientists call isoforms. This dramatically increases the complexity of our genome, so that fewer genes are needed to encode all the proteins a cell needs.

“When mRNAs leave the nucleus and move to the cytoplasm, they need to be properly directed to reach the appropriate site of protein translation,” said Dr. Bin Tian. “The cytoplasm is a huge space for an RNA molecule: For comparison, imagine entering a baseball stadium and needing directions to reach your seat.”

Researchers discovered that APA directs certain messenger RNAs to the endoplasmic reticulum (ER), a network of tubes that build, package and transport proteins. They also found that specific sequences and structures within the messenger RNAs determine their potential to undergo APA and ultimately associate with the ER.

These mRNAs tend to encode for signaling proteins, which help cells communicate with each other by sending, receiving, and processing signals in response to changes in the environment.

Dr. Tian and his team hypothesize that association with the ER anchors certain mRNA isoforms in specific cellular locations where important signaling events happen, making the whole process more efficient.

Reference:  Alternative 3’UTRs play a widespread role in translation-independent mRNA association with endoplasmic reticulum, Cell Reports (2021).