Tent2, also known as PAPD4 or GLD2, is a terminal nucleotidyltransferase involved in RNA 3' end tailing, an important post-transcriptional mechanism regulating RNA stability. It participates in the addition of non-templated nucleotides to the 3' ends of RNA molecules, contributing to processes such as miRNA biogenesis and regulation, and is involved in maintaining the balance of excitatory and inhibitory neurotransmission [1,2].

A Tent2 knockout mouse model revealed increased excitability in hippocampal neurons, decreased anxiety, and improved fear extinction in these mice. At the molecular level, changes in miRNAs monoadenylation were observed in the Tent2 KO mouse hippocampus, but no effect on the mRNAs total poly(A) tail length was found. Also, transcripts related to synaptic transmission were downregulated in the hippocampus of Tent2 knockout mice, suggesting a link between TENT2-dependent miRNA tailing and the balance of inhibitory and excitatory neurotransmission [2].

In addition, in HEK293T cell lines, TENT2 was found to contribute to guanylation and uridylation on mature miRNAs in addition to its known adenylation function, and removing adenylation had a marginal impact on miRNA levels, while abolishing uridylation led to dysregulation of a set of miRNAs [1].

In conclusion, Tent2 plays essential roles in miRNA sequence and abundance regulation as well as in maintaining the excitatory/inhibitory balance in the hippocampus. The Tent2 KO mouse model has been crucial in revealing these functions, which could potentially contribute to understanding and treating conditions related to miRNA dysregulation and neural excitability-related disorders.