Microproteins: from behind the scenes to the spotlight

Jiang, Meiqian; Lou, Huiqiang; Hou, Wenya

doi:10.1007/s42764-021-00040-3

Cited by 6 publications

(4 citation statements)

References 132 publications

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“…There are many definitions of sORF-encoded proteins . Sometimes SEPs and microproteins are the same, while in some cases, SEPs refer to noncanonical and unannotated microproteins.…”

Section: Resultsmentioning

confidence: 99%

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Systematic Identification of Microproteins during the Development of Drosophila melanogaster

Wang

Yan

et al. 2022

J. Proteome Res.

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Short open reading frame-encoded peptides (SEPs) are microproteins with less than 100 amino acids that play an essential role in the growth and development of organisms. There are plenty of short open reading frames in Drosophila melanogaster that potentially code polypeptides. We chose 11 time points during the life cycle of Drosophila to investigate microproteins, particularly those related to development. Finally, we identified a total of 410 microproteins, of which 27 were noncoding RNAencoded proteins. Of the 410 microproteins, 74 were expressed in all stages from embryo to adults, whereas 300 microproteins were only found in one or two time points. Approximately, one-third of the microproteins were not reported previously and 44 were obtained from de novo sequencing, validated by synthetic peptides. These microproteins are related to the main bioprocesses of growth and development, such as multicellular organism reproduction, postmating behavior, and oviposition. Over half of the microproteins have predicted functional domains and are conserved across species, suggesting that these microproteins have critical functions in fly development. This work enriches the D. melanogaster proteome and provides a significant data resource for growth and development research.

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“…There are many definitions of sORF-encoded proteins . Sometimes SEPs and microproteins are the same, while in some cases, SEPs refer to noncanonical and unannotated microproteins.…”

Section: Resultsmentioning

confidence: 99%

“…There are many definitions of sORF-encoded proteins. 26 Sometimes SEPs and microproteins are the same, while in some cases, SEPs refer to noncanonical and unannotated microproteins. In this work, microproteins refer to small proteins of less than 100 AAs, including novel SEPs and canonical small proteins.…”

Section: Workflow To Identify Drosophila Microproteinsmentioning

confidence: 99%

Systematic Identification of Microproteins during the Development of Drosophila melanogaster

Wang

Yan

et al. 2022

J. Proteome Res.

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“…Small proteins have considerable advantages over larger ones: their genes are easier to synthesize, they take up fewer cell resources to express, they can be engineered to be highly stable, and they are potentially able to penetrate into tissues and cells. [46][47][48] In the context of catalysis, smaller enzymes duplicate the desired catalytic activity using just the necessary residues and may benefit the costeffectiveness of industrial applications. In this study, we intentionally generate new designs with shorter amino acid sequences compared to the original enzyme.…”

Section: Discussionmentioning

confidence: 99%

Replicating enzymatic activity by positioning active sites with synthetic protein scaffolds

Ding,

Zhang,

Hess

et al. 2024

Preprint

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Evolutionary constraints significantly limit the diversity of naturally occurring enzymes, thereby reducing the sequence repertoire available for enzyme discovery and engineering. Recent breakthroughs in protein structure prediction and de novo design, powered by artificial intelligence, now enable us to create enzymes with desired functions without relying on traditional genome mining. Here, we demonstrate a computational strategy for creating new-to-nature PET hydrolases by leveraging the known catalytic mechanisms and implementing multiple deep learning algorithms and molecular computations. This strategy includes the extraction of functional motifs from a template enzyme (here we use leaf-branch compost cutinase, LCC), regeneration of new protein scaffolds, computational screening, experimental validation, and sequence refinement. We successfully replicate PET hydrolytic activity with designer enzymes that are at least 30% shorter in sequence length than LCC. Among them, RsPETase 1 stands out due to its robust expressibility. It exhibits comparable activity to IsPETase and considerable thermostability with a melting temperature of 56 °C, despite sharing only 34% sequence similarity with LCC. This work suggests that enzyme diversity can be expanded by recapitulating functional motifs with computationally built protein scaffolds, thus generating opportunities to acquire highly active and robust enzymes that do not exist in nature.

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“…With recent advancements in ribosome profiling methods, mass spectrometry and algorithms to analyse the resulting data, a large number of peptides arising from non-canonical ORFs are being detected. These ORFs and peptides have been referred to variously, based on their size (microproteins), origin (smORFs, altORFs), structure (cyclotides) and often inhibitory role (miPs, ID proteins) (Jiang, Lou, and Hou 2021).…”

Section: Introductionmentioning

confidence: 99%

SMIM36, a novel and conserved microprotein, is involved in retinal lamination in zebrafish

Sharma

Ramasamy

Khan

et al. 2023

Preprint

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Microproteins are small proteins comprising 2 to 200 amino acids, arising from small Open Reading Frames (smORFs). They are found in different parts of the cell and regulate basic molecular processes like DNA replication, repair, transcription and recombination. SMIM or SMall Integral Membrane proteins are novel, largely uncharacterized, members to the class of microproteins defined by the presence of a transmembrane domain. The retinal transcriptome of zebrafish, reported previously by our group, revealed several novel mRNA transcripts that show oscillating expression in a diurnal manner. Here, we show that one of these transcripts encodes the zebrafish homolog of the human SMIM36 protein, which has not been functionally characterised. This highly conserved microprotein is expressed in the human and zebrafish retina, and efficiently translated in cell lines. Using single-cell RNA-seq datasets, we found that it is expressed in the bipolar cells, rods and Muller glia in the human retina. The knockdown of SMIM36 using splice-block morpholino caused microphthalmia and defects in the retinal layers in zebrafish. Therefore, we show the role of a microprotein in the neural retina thus paving the way for future studies on the role of SMIM proteins in retinal disorders.

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Microproteins: from behind the scenes to the spotlight

Cited by 6 publications

References 132 publications

Systematic Identification of Microproteins during the Development of Drosophila melanogaster

Systematic Identification of Microproteins during the Development of Drosophila melanogaster

Replicating enzymatic activity by positioning active sites with synthetic protein scaffolds

SMIM36, a novel and conserved microprotein, is involved in retinal lamination in zebrafish

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