The Essentials on microRNA-Encoded Peptides from Plants to Animals

Abstract

Primary transcripts of microRNAs (pri-miRNAs) were initially defined as long non-coding RNAs that host miRNAs further processed by the microRNA processor complex. A few years ago, however, it was discovered in plants that pri-miRNAs actually contain functional open reading frames (sORFs) that translate into small peptides called miPEPs, for microRNA-encoded peptides. Initially detected in Arabidopsis thaliana and Medicago truncatula, recent studies have revealed the presence of miPEPs in other pri-miRNAs as well as in other species ranging from various plant species to animals. This suggests that miPEP numbers remain largely underestimated and that they could be a common signature of pri-miRNAs. Here we present the most recent advances in miPEPs research and discuss how their discovery has broadened our vision of the regulation of gene expression by miRNAs, and how miPEPs could be interesting tools in sustainable agriculture or the treatment of certain human diseases.

Biological Activity of Artificial Plant Peptides Corresponding to the Translational Products of Small ORFs in Primary miRNAs and Other Long “Non-Coding” RNAs

“…In planta interaction of peptides Mt-miPEP171b and sequence-unrelated Mt-miPEP171b2 to their common nascent pri-miRNA molecules has been shown by microscopic method (FRET-FLIM) and isothermal titration calorimetry. It has been suggested that this kind of protein–RNA binding strongly depends on the presence of a specific linear set of codons encoding interacting miPEP, but not a strongly conserved nucleotide sequence, so that non-conserved miPEPs can perform specific regulatory functions on their pri-miRNA species only [ 30 , 55 ].…”

“…Assuming the peculiarities of interaction between miPEPs and their nascent pri-miRNAs [ 30 , 55 ], the following scheme for activation of pri-miRNAs by the encoded peptides has been proposed: miPEP translates in the cytoplasm from the full-length pri-miRNA or its fragment, containing ORF encoding miPEP; then, this peptide migrates to the nucleus, where it binds to the nascent pri-miRNA in the area of its coding sequence; such interaction further activates synthesis of the miRNA transcript at the transcription level [ 30 , 55 ]. However, the authors stress that there are some unanswered questions concerning the proposed mechanism.…”

“…Is the only interaction between miPEPs and their corresponding miORFs sufficient? Are regulatory proteins necessary for miPEP action and/or specificity, and, if so, which ones?” [ 30 ].…”

“…Recent studies have shown that the short open reading frames (sORFs) of some plant lncRNAs encode functional small peptides (micropeptides) with a size of around 5 to 100 amino acids [ 10 , 12 , 17 , 18 , 19 , 20 , 21 , 22 ]. Importantly, these lncRNAs also include precursors of many microRNAs, which code for peptides called miPEPs (peptides encoded by primary microRNAs), and some trans-acting siRNAs [ 19 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. Currently, bioinformatic tools as well as experimental methods such as mass spectrometry, ribosome mapping and in vitro translation are used to reveal the potential translational products of lncRNAs [ 10 , 16 , 17 , 19 , 21 , 24 , 32 , 35 , 36 , 37 , 38 , 39 ].…”

Small but mighty: Peptides regulating abiotic stress responses in plants

“…Plant peptides are synthesized from precursor proteins or small open reading frames (sORFs) embedded within transcripts. These sORFs comprise 100 codons or less and lie either in the 5′‐leader sequence of a messenger RNA or are embedded within the primary transcripts of microRNAs (miRNAs) or are present within transcripts that code for short proteins of length <100 amino acids (Gautam et al, 2023; Hanada et al, 2013; Kumar et al, 2023; Lauressergues et al, 2015; Lauressergues et al, 2022; Ormancey et al, 2023; Sharma et al, 2020; Von Arnim et al, 2014).…”