# LncRNA-Encoded Micropeptides: Expression Validation, Translational Mechanisms, and Roles in Cellular Metabolism

**Authors:** Chul Woong Ho, Ji Won Lee, Chang Hoon Shin, Kyung-Won Min

PMC · DOI: 10.3390/ijms26125913 · International Journal of Molecular Sciences · 2025-06-19

## TL;DR

This review explores how micropeptides from long noncoding RNAs affect cellular metabolism and the challenges in studying them.

## Contribution

The paper provides a comprehensive overview of the biogenesis, detection, and metabolic roles of lncRNA-encoded micropeptides.

## Key findings

- LncRNAs can encode bioactive micropeptides that influence cellular metabolism.
- High-resolution translation profiling and MS-based techniques are key for identifying these micropeptides.
- Micropeptides modulate enzymatic activity and metabolic pathways, with implications in health and disease.

## Abstract

The discovery of functional micropeptides encoded by long noncoding RNAs (lncRNAs) has challenged the traditional view that these transcripts lack coding potential. With the advancement of high-resolution translation profiling combined with enhanced MS-based techniques, numerous lncRNAs have been found to harbor small open reading frames (sORFs) that give rise to bioactive micropeptides. These peptides participate in diverse biological processes, particularly in cellular metabolism, by modulating enzymatic activity and metabolic pathways. However, the identification and functional characterization of these micropeptides remain technically challenging due to their small size, low abundance, and the need for rigorous downstream validation studies. This review encompasses a comprehensive overview of the biogenesis of lncRNA-derived micropeptides, methodologies for detecting and validating their expression, the molecular mechanisms governing their translation, and their emerging roles in metabolic regulation. By integrating current findings and technological advancements, we highlight the potential physiological and pathological implications of these micropeptides and outline future research directions in the field.

## Full-text entities

- **Genes:** HNRNPA2B1 (heterogeneous nuclear ribonucleoprotein A2/B1) [NCBI Gene 3181] {aka HNRNPA2, HNRNPB1, HNRPA2, HNRPA2B1, HNRPB1, IBMPFD2}, C11orf98 (chromosome 11 open reading frame 98) [NCBI Gene 102288414] {aka C11orf48}, WTAP (WT1 associated protein) [NCBI Gene 9589] {aka Mum2}, Slc2a1 (solute carrier family 2 (facilitated glucose transporter), member 1) [NCBI Gene 20525] {aka GT1, Glut-1, Glut1, M100200, Rgsc200}, GPX4 (glutathione peroxidase 4) [NCBI Gene 2879] {aka GPx-4, GSHPx-4, MCSP, PHGPx, SMDS, snGPx}, TALDO1 (transaldolase 1) [NCBI Gene 6888] {aka TAL, TAL-H, TALDOR, TALH}, RAD51C (RAD51 paralog C) [NCBI Gene 5889] {aka BROVCA3, FANCO, R51H3, RAD51L2}, CTBP1 (C-terminal binding protein 1) [NCBI Gene 1487] {aka BARS, HADDTS}, RN7SL1 (RNA component of signal recognition particle 7SL1) [NCBI Gene 6029] {aka 7L1a, 7SL, RN7SL, RNSRP1}, YTHDF3 (YTH N6-methyladenosine RNA binding protein F3) [NCBI Gene 253943] {aka DF3}, H19 (H19 imprinted maternally expressed transcript) [NCBI Gene 283120] {aka ASM, ASM1, BWS, D11S813E, GMRSP, LINC00008}, Nodal (nodal growth differentiation factor) [NCBI Gene 18119] {aka Tg.413d}, MTLN (mitoregulin) [NCBI Gene 205251] {aka LEMP, LINC00116, MOXI, MPM, NCRNA00116, SMIM37}, AFAP1-AS1 (AFAP1 antisense RNA 1) [NCBI Gene 84740] {aka AFAP1-AS, AFAP1AS, ATMLP}, ALKBH5 (alkB homolog 5, RNA demethylase) [NCBI Gene 54890] {aka ABH5, OFOXD, OFOXD1}, PKM (pyruvate kinase M1/2) [NCBI Gene 5315] {aka CTHBP, HEL-S-30, OIP3, PK3, PKM2, TCB}, PAEP (progestagen associated endometrial protein) [NCBI Gene 5047] {aka GD, GdA, GdF, GdS, PAEG, PEP}, SRP19 (signal recognition particle 19) [NCBI Gene 6728], Smim43 (small integral membrane protein 43) [NCBI Gene 100503068] {aka Gm11549, NEMEP}, YTHDF1 (YTH N6-methyladenosine RNA binding protein F1) [NCBI Gene 54915] {aka C20orf21, DF1}, PCNA (proliferating cell nuclear antigen) [NCBI Gene 5111] {aka ATLD2}, MST1 (macrophage stimulating 1) [NCBI Gene 4485] {aka D3F15S2, DNF15S2, HGFL, MSP, NF15S2}, LINC00689 (long intergenic non-protein coding RNA 689) [NCBI Gene 154822] {aka STORM}, HOXB-AS3 (HOXB cluster antisense RNA 3) [NCBI Gene 404266], CSE1L (chromosome segregation 1 like) [NCBI Gene 1434] {aka CAS, CSE1, XPO2}, ATP5F1C (ATP synthase F1 subunit gamma) [NCBI Gene 509] {aka ATP5C, ATP5C1, ATP5CL1}, NUCLEOLIN (nucleolin multifunctional protein) [NCBI Gene 4691] {aka C23, NCL, Nsr1}, EIF4E (eukaryotic translation initiation factor 4E) [NCBI Gene 1977] {aka AUTS19, CBP, EIF4E1, EIF4EL1, EIF4F, eIF-4E}, AKR1C2 (aldo-keto reductase family 1 member C2) [NCBI Gene 1646] {aka AKR1C-pseudo, BABP, DD, DD-2, DD/BABP, DD2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CPT1B (carnitine palmitoyltransferase 1B) [NCBI Gene 1375] {aka CPT1-M, CPT1M, CPTI, CPTI-M, M-CPT1, MCCPT1}, ATP5PF (ATP synthase peripheral stalk subunit F6) [NCBI Gene 522] {aka ATP5, ATP5A, ATP5J, ATPM, CF6, F6}, CPT1A (carnitine palmitoyltransferase 1A) [NCBI Gene 1374] {aka CPT I, CPT1, CPT1-L, CPTI-L, L-CPT1}, APEX2 (apurinic/apyrimidinic endodeoxyribonuclease 2) [NCBI Gene 27301] {aka APE2, APEXL2, XTH2, ZGRF2}, CYB5B (cytochrome b5 type B) [NCBI Gene 80777] {aka CYB5-M, CYPB5M, OMB5}, LINC00278 (long intergenic non-protein coding RNA 278) [NCBI Gene 100873962] {aka NCRNA00278, YY1BM}, RAD18 (RAD18 E3 ubiquitin protein ligase) [NCBI Gene 56852] {aka RNF73}, EIF3A (eukaryotic translation initiation factor 3 subunit A) [NCBI Gene 8661] {aka EIF3, EIF3S10, P167, TIF32, eIF3-p170, eIF3-theta}, METTL3 (methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit) [NCBI Gene 56339] {aka IME4, M6A, MT-A70, Spo8, hMETTL3}, METTL14 (methyltransferase 14, N6-adenosine-methyltransferase non-catalytic subunit) [NCBI Gene 57721] {aka hMETTL14}, LINC00467 (long intergenic non-protein coding RNA 467) [NCBI Gene 84791] {aka ASAP, C1orf97}, NPM1 (nucleophosmin 1) [NCBI Gene 4869] {aka B23, NPM}, HNRNPA1 (heterogeneous nuclear ribonucleoprotein A1) [NCBI Gene 3178] {aka ALS19, ALS20, HNRPA1, HNRPA1L3, IBMPFD3, MPD3}, HCP5 (HLA complex P5) [NCBI Gene 10866] {aka 6S2650E, D6S2650E, P5-1}, Slc2a3 (solute carrier family 2 (facilitated glucose transporter), member 3) [NCBI Gene 20527] {aka Glut-3, Glut3}, SPAAR (small regulatory polypeptide of amino acid response) [NCBI Gene 158376] {aka LINC00961, SPAR}, YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}
- **Diseases:** ovarian cancer (MESH:D010051), GC (MESH:D013274), CRC (MESH:D015179), TNBC (MESH:D064726), injury to (MESH:D014947), NSCLC (MESH:D002289), LNM (MESH:D008207), ESCC (MESH:D000077277), cancer (MESH:D009369)
- **Chemicals:** ribose-5-phosphate (MESH:C031626), GSH (MESH:D005978), N6-methyladenosine (MESH:C010223), iron (MESH:D007501), ATP (MESH:D000255), Glucose (MESH:D005947), NADH (MESH:D009243), pyruvate (MESH:D019289), oxygen (MESH:D010100), pentose phosphate (MESH:D010428), VLCFAs (MESH:C017364), ASAP (-), ROS (MESH:D017382), Oxaliplatin (MESH:D000077150), lipid (MESH:D008055), phosphoenolpyruvate (MESH:D010728), nucleotide (MESH:D009711), STORM (MESH:C048069), NADPH (MESH:D009249), fatty acid (MESH:D005227), lactate (MESH:D019344), DHA (MESH:D004281), micropeptides (MESH:C000722334), Amino Acids (MESH:D000596), proline (MESH:D011392)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** R5P

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12192620/full.md

## References

101 references — full list in the complete paper: https://tomesphere.com/paper/PMC12192620/full.md

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Source: https://tomesphere.com/paper/PMC12192620