The Small Open Reading Frame‐Encoded Peptides: Advances in Methodologies and Functional Studies

Chen, Lei; Yang, Ying; Zhang, Yuanliang; Li, Kecheng; Cai, Hongmin; Wang, Yan; Zhao, Qian

doi:10.1002/cbic.202100534

Cited by 6 publications

(7 citation statements)

References 173 publications

(272 reference statements)

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“…It turned out that only four of these proteins were folded and one protein was partially folded, whereas the majority of proteins were in the molten globule state, were totally unfolded, or could not be produced. Various reviews summarize the specific challenges in the heterologous or homologous production of μ-proteins, in contrast to average-sized proteins ( Storz et al, 2014 ; Orr et al, 2020 ; Cassidy et al, 2021 ; Steinberg and Koch, 2021 ; Tharakan and Sawa, 2021 ; Chen et al, 2022 ; Gray et al, 2022 ; Leong et al, 2022 ; Schlesinger and Elsässer, 2022 ; Weidenbach et al, 2022 ; Zhang et al, 2022 ; Dong et al, 2023 ; Hassel et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

“…Notable advancements encompass the establishment of ribosome profiling methods, advances in mass spectrometry (peptidomics), and enhancements in gene/ORF prediction through bioinformatics refinements. Several recent reviews summarize current knowledge about very small proteins in archaea, bacteria, and eukaryotes ( Storz et al, 2014 ; Orr et al, 2020 ; Cassidy et al, 2021 ; Steinberg and Koch, 2021 ; Tharakan and Sawa, 2021 ; Chen et al, 2022 ; Gray et al, 2022 ; Leong et al, 2022 ; Schlesinger and Elsässer, 2022 ; Weidenbach et al, 2022 ; Zhang et al, 2022 ; Dong et al, 2023 ; Hassel et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

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Characterization of the zinc finger μ-protein HVO_0758 from Haloferax volcanii: biological roles, zinc binding, and NMR solution structure

Üresin,

Pyper,

Borst

et al. 2023

Front. Microbiol.

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It is increasingly recognized that very small proteins (μ-proteins) are ubiquitously found in all species of the three domains of life, and that they fulfill important functions. The halophilic archaeon Haloferax volcanii contains 282 μ-proteins of less than 70 amino acids. Notably, 43 of these contain two C(P)XCG motifs, suggesting their potential to complex a zinc ion. To explore the significance of these proteins, 16 genes encoding C(P)XCG proteins had been deleted, and the majority of mutants exhibited phenotypic differences to the wild-type. One such protein, HVO_2753, was thoroughly characterized in a previous study. In the present study an in-depth analysis of a second protein, HVO_0758, was performed. To achieve this goal, the HVO_0758 protein was produced heterologously in Escherichia coli and homologously in H. volcanii. The purified protein was characterized using various biochemical approaches and NMR spectroscopy. The findings demonstrated that HVO_0758 is indeed a bona fide zinc finger protein, and that all four cysteine residues are essential for folding. The NMR solution structure was solved, revealing that HVO_0758 is comprised of an N-terminal alpha helix containing several positively charged residues and a globular core with the zinc finger domain. The transcriptomes of the HVO_0758 deletion mutant and, for comparison, the HVO_2753 deletion mutant were analyzed with RNA-Seq and compared against that of the wild-type. In both mutants many motility and chemotaxis genes were down-regulated, in agreement to the phenotype of the deletion mutants, which had a swarming deficit. The two H. volcanii zinc-finger μ-proteins HVO_0758 and HVO_2753 showed many differences. Taken together, two zinc finger μ-proteins of H. volcanii have been characterized intensively, which emerged as pivotal contributors to swarming behavior and biofilm formation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of the zinc finger μ-protein HVO_0758 from Haloferax volcanii: biological roles, zinc binding, and NMR solution structure

Üresin,

Pyper,

Borst

et al. 2023

Front. Microbiol.

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“…C8-SPE is another method based on hydrophilic and hydrophobic properties of SEPs [ 66 ]. It was reported that a combination of these methods may be able to identify more SEPs [ 71 ].…”

Section: Peptidomic-based Methodology For Identification Of Sepsmentioning

confidence: 99%

Small Open Reading Frame-Encoded Micro-Peptides: An Emerging Protein World

Dong

Zhang

Xun

et al. 2023

IJMS

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Small open reading frames (sORFs) are often overlooked features in genomes. In the past, they were labeled as noncoding or “transcriptional noise”. However, accumulating evidence from recent years suggests that sORFs may be transcribed and translated to produce sORF-encoded polypeptides (SEPs) with less than 100 amino acids. The vigorous development of computational algorithms, ribosome profiling, and peptidome has facilitated the prediction and identification of many new SEPs. These SEPs were revealed to be involved in a wide range of basic biological processes, such as gene expression regulation, embryonic development, cellular metabolism, inflammation, and even carcinogenesis. To effectively understand the potential biological functions of SEPs, we discuss the history and development of the newly emerging research on sORFs and SEPs. In particular, we review a range of recently discovered bioinformatics tools for identifying, predicting, and validating SEPs as well as a variety of biochemical experiments for characterizing SEP functions. Lastly, this review underlines the challenges and future directions in identifying and validating sORFs and their encoded micropeptides, providing a significant reference for upcoming research on sORF-encoded peptides.

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“…Therefore, a small portion of smORFs have the potential to be translated into polypeptides ( Wu et al, 2019 ; Ladoukakis et al, 2011 ). These peptides with lengths less than 100 amino acids are called micro-peptides or smORF-encoded peptides (SEPs) ( Chen et al, 2021 ). Further studies on micro-peptides based on bioinformatics and high-throughput sequencing technology have found that micro-peptides not only are highly conserved throughout evolution ( Ladoukakis et al, 2011 ) but also play an important regulatory role in a series of processes such as biological development ( Sanchez-Ortiz, 2017 ; Read et al, 2019 ), metabolism ( Makarewich et al, 2018 ; Stein et al, 2018 ), and cancer incidence ( Pang et al, 2020 ; Wu et al, 2020 ; Li et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Systematic identification of smORFs in domestic silkworm (Bombyx mori)

Wan

Xiao

Huang³

et al. 2023

PeerJ

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The silkworm (Bombyx mori) is not only an excellent model species, but also an important agricultural economic insect. Taking it as the research object, its advantages of low maintenance cost and no biohazard risks are considered. Small open reading frames (smORFs) are an important class of genomic elements that can produce bioactive peptides. However, the smORFs in silkworm had been poorly identified and studied. To further study the smORFs in silkworm, systematic genome-wide identification is essential. Here, we identified and analyzed smORFs in the silkworm using comprehensive methods. Our results showed that at least 738 highly reliable smORFs were found in B. mori and that 34,401 possible smORFs were partially supported. We also identified some differentially expressed and tissue-specific-expressed smORFs, which may be closely related to the characteristics and functions of the tissues. This article provides a basis for subsequent research on smORFs in silkworm, and also hopes to provide a reference point for future research methods for smORFs in other species.

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The Small Open Reading Frame‐Encoded Peptides: Advances in Methodologies and Functional Studies

Cited by 6 publications

References 173 publications

Characterization of the zinc finger μ-protein HVO_0758 from Haloferax volcanii: biological roles, zinc binding, and NMR solution structure

Characterization of the zinc finger μ-protein HVO_0758 from Haloferax volcanii: biological roles, zinc binding, and NMR solution structure

Small Open Reading Frame-Encoded Micro-Peptides: An Emerging Protein World

Systematic identification of smORFs in domestic silkworm (Bombyx mori)

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