The dual role of N6-methyladenosine on mouse maternal RNAs and 2-cell specific RNAs revealed by ULI-MeRIP sequencing

N6-methyladenosine (m6A) and its regulatory components play critical roles in various developmental processes in mammals(1-5). However, the landscape and function of m6A in the maternal-to-zygotic transition (MZT) remain unclear due to limited materials. Here, by developing an ultralow-input MeRIP-seq method, we revealed the dynamics of the m6A RNA methylome during the MZT process in mice. We found that more than 1/3 maternal decay and 2/3 zygotic mRNAs were modified by m6A. Moreover, m6As are highly enriched in the RNA of transposable elements MTA and MERVL, which are highly expressed in oocytes and 2-cell embryos, respectively. Notably, maternal depletion of Kiaa1429, a component of the m6A methyltransferase complex, leads to a reduced abundance of m6A-marked maternal RNAs, including both genes and MTA, in GV oocytes, indicating m6A-dependent regulation of RNA stability in oocytes. Interestingly, when the writers were depleted, some m6A-marked 2-cell specific RNAs, including Zscan4 and MERVL, appeared normal at the 2-cell stage but failed to be decayed at later stages, suggesting that m6A regulates the clearance of these transcripts. Together, our study uncovered that m6As function in context-specific manners during MZT, which ensures the transcriptome stability of oocytes and regulates the stage specificity of zygotic transcripts after fertilization.

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Role of Axonal Odorant Receptors in Olfactory Topography

Neuroscience Insights ◽

10.1177/2633105520923411 ◽

2020 ◽

Vol 15 ◽

pp. 263310552092341

Author(s):

Claudia Lodovichi

Keyword(s):

Olfactory Bulb ◽

Sensory Neurons ◽

Axon Terminal ◽

Internal Representation ◽

Dual Role ◽

Odorant Receptors ◽

Topographic Map ◽

And Function ◽

Guidance Molecule

A unique feature in the organization of the olfactory system is the dual role of the odorant receptors: they detect odors in the nasal epithelium and they play an instructive role in the convergence of olfactory sensory neuron axons in specific loci, ie, glomeruli, in the olfactory bulb. The dual role is corroborated by the expression of the odorant receptors in 2 specific locations of the olfactory sensory neurons: the cilia that protrude in the nostril, where the odorant receptors interact with odors, and the axon terminal, a suitable location for a potential axon guidance molecule. The mechanism of activation and function of the odorant receptors expressed at the axon terminal remained unknown for almost 20 years. A recent study identified the first putative ligand of the axonal odorant receptors, phosphatidylethanolamine-binding protein1, a molecule expressed in the olfactory bulb. The distinctive mechanisms of activation of the odorant receptors expressed at the opposite locations in sensory neurons, by odors, at the cilia, and by molecules expressed in the olfactory bulb, at the axon terminal, explain the dual role of the odorant receptors and link the specificity of odor perception with its internal representation, in the topographic map.

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Do Plasmodesmata Play a Prominent Role in Regulation of Auxin-Dependent Genes at Early Stages of Embryogenesis?

Cells ◽

10.3390/cells10040733 ◽

2021 ◽

Vol 10 (4) ◽

pp. 733

Author(s):

Konrad Winnicki ◽

Justyna Teresa Polit ◽

Aneta Żabka ◽

Janusz Maszewski

Keyword(s):

Gene Expression ◽

Regulation Of Gene Expression ◽

High Permeability ◽

Cell Stage ◽

Developmental Processes ◽

Early Stages ◽

Cellular Patterning ◽

Intercellular Channels ◽

Auxin Efflux Carriers

Plasmodesmata form intercellular channels which ensure the transport of various molecules during embryogenesis and postembryonic growth. However, high permeability of plasmodesmata may interfere with the establishment of auxin maxima, which are required for cellular patterning and the development of distinct tissues. Therefore, diffusion through plasmodesmata is not always desirable and the symplastic continuum must be broken up to induce or accomplish some developmental processes. Many data show the role of auxin maxima in the regulation of auxin-responsive genes and the establishment of various cellular patterns. However, still little is known whether and how these maxima are formed in the embryo proper before 16-cell stage, that is, when there is still a nonpolar distribution of auxin efflux carriers. In this work, we focused on auxin-dependent regulation of plasmodesmata function, which may provide rapid and transient changes of their permeability, and thus take part in the regulation of gene expression.

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Maternally provided LSD1/KDM1A enables the maternal-to-zygotic transition and prevents defects that manifest postnatally

eLife ◽

10.7554/elife.08848 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 48

Author(s):

Jadiel A Wasson ◽

Ashley K Simon ◽

Dexter A Myrick ◽

Gernot Wolf ◽

Shawn Driscoll ◽

...

Keyword(s):

Epigenetic Reprogramming ◽

Abnormal Behavior ◽

Maternal Factors ◽

Partial Loss ◽

Cell Stage ◽

C Elegans ◽

Maternal To Zygotic Transition ◽

Perinatal Lethality ◽

And Function ◽

Embryonic Arrest

Somatic cell nuclear transfer has established that the oocyte contains maternal factors with epigenetic reprogramming capacity. Yet the identity and function of these maternal factors during the gamete to embryo transition remains poorly understood. In C. elegans, LSD1/KDM1A enables this transition by removing H3K4me2 and preventing the transgenerational inheritance of transcription patterns. Here we show that loss of maternal LSD1/KDM1A in mice results in embryonic arrest at the 1-2 cell stage, with arrested embryos failing to undergo the maternal-to-zygotic transition. This suggests that LSD1/KDM1A maternal reprogramming is conserved. Moreover, partial loss of maternal LSD1/KDM1A results in striking phenotypes weeks after fertilization; including perinatal lethality and abnormal behavior in surviving adults. These maternal effect hypomorphic phenotypes are associated with alterations in DNA methylation and expression at imprinted genes. These results establish a novel mammalian paradigm where defects in early epigenetic reprogramming can lead to defects that manifest later in development.

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Scanning electron microscopic study of collagen fibrillogenesis and extracellular compartmentalization in the chick embryo tendon

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100142669 ◽

1986 ◽

Vol 44 ◽

pp. 208-209

Author(s):

Grace C.H. Yang

Keyword(s):

Chick Embryo ◽

Extracellular Space ◽

Fibroblast Cell ◽

Collagen Fibrils ◽

Electron Microscopic ◽

Voltage Electron ◽

Scanning Electron Microscopic Study ◽

Microscopic Studies ◽

And Function

The size and organization of collagen fibrils in the extracellular matrix is an important determinant of tissue structure and function. The synthesis and deposition of collagen involves multiple steps which begin within the cell and continue in the extracellular space. High-voltage electron microscopic studies of the chick embryo cornea and tendon suggested that the extracellular space is compartmentalized by the fibroblasts for the regulation of collagen fibril, bundle, and tissue specific macroaggregate formation. The purpose of this study is to gather direct evidence regarding the association of the fibroblast cell surface with newly formed collagen fibrils, and to define the role of the fibroblast in the control and the precise positioning of collagen fibrils, bundles, and macroaggregates during chick tendon development.

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Role of the Cilia Membrane in Control of Microtubule Sliding

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600002683 ◽

1980 ◽

Vol 38 ◽

pp. 612-615

Author(s):

Edna S. Kaneshiro

Keyword(s):

Control Mechanism ◽

Beat Frequency ◽

Surface Membrane ◽

Ciliary Membrane ◽

Ciliary Beating ◽

Ciliary Reversal ◽

Voltage Dependent ◽

Reversal Mechanism ◽

And Function

It is currently believed that ciliary beating results from microtubule sliding which is restricted in regions to cause bending. Cilia beat can be modified to bring about changes in beat frequency, cessation of beat and reversal in beat direction. In ciliated protozoans these modifications which determine swimming behavior have been shown to be related to intracellular (intraciliary) Ca2+ concentrations. The Ca2+ levels are in turn governed by the surface ciliary membrane which exhibits increased Ca2+ conductance (permeability) in response to depolarization. Mutants with altered behaviors have been isolated. Pawn mutants fail to exhibit reversal of the effective stroke of ciliary beat and therefore cannot swim backward. They lack the increased inward Ca2+ current in response to depolarizing stimuli. Both normal and pawn Paramecium made leaky to Ca2+ by Triton extrac¬tion of the surface membrane exhibit backward swimming only in reactivating solutions containing greater than IO-6 M Ca2+ Thus in pawns the ciliary reversal mechanism itself is left operational and only the control mechanism at the membrane is affected. The topographic location of voltage-dependent Ca2+ channels has been identified as a component of the ciliary mem¬brane since the inward Ca2+ conductance response is eliminated by deciliation and the return of the response occurs during cilia regeneration. Since the ciliary membrane has been impli¬cated in the control of Ca2+ levels in the cilium and therefore is the site of at least one kind of control of microtubule sliding, we have focused our attention on understanding the structure and function of the membrane.

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Role of small nuclear RNAs in eukaryotic gene expression

Essays in Biochemistry ◽

10.1042/bse0540079 ◽

2013 ◽

Vol 54 ◽

pp. 79-90 ◽

Cited By ~ 34

Author(s):

Saba Valadkhan ◽

Lalith S. Gunawardane

Keyword(s):

Gene Expression ◽

Protein Interactions ◽

Rna Stability ◽

Splice Sites ◽

Branch Site ◽

Small Nuclear Rnas ◽

Eukaryotic Gene Expression ◽

Eukaryotic Gene ◽

Rna Biogenesis

Eukaryotic cells contain small, highly abundant, nuclear-localized non-coding RNAs [snRNAs (small nuclear RNAs)] which play important roles in splicing of introns from primary genomic transcripts. Through a combination of RNA–RNA and RNA–protein interactions, two of the snRNPs, U1 and U2, recognize the splice sites and the branch site of introns. A complex remodelling of RNA–RNA and protein-based interactions follows, resulting in the assembly of catalytically competent spliceosomes, in which the snRNAs and their bound proteins play central roles. This process involves formation of extensive base-pairing interactions between U2 and U6, U6 and the 5′ splice site, and U5 and the exonic sequences immediately adjacent to the 5′ and 3′ splice sites. Thus RNA–RNA interactions involving U2, U5 and U6 help position the reacting groups of the first and second steps of splicing. In addition, U6 is also thought to participate in formation of the spliceosomal active site. Furthermore, emerging evidence suggests additional roles for snRNAs in regulation of various aspects of RNA biogenesis, from transcription to polyadenylation and RNA stability. These snRNP-mediated regulatory roles probably serve to ensure the co-ordination of the different processes involved in biogenesis of RNAs and point to the central importance of snRNAs in eukaryotic gene expression.

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POPDC proteins and cardiac function

Biochemical Society Transactions ◽

10.1042/bst20190249 ◽

2019 ◽

Vol 47 (5) ◽

pp. 1393-1404 ◽

Cited By ~ 4

Author(s):

Thomas Brand

Keyword(s):

Potential Role ◽

Striated Muscle ◽

Short Review ◽

Effector Proteins ◽

Muscle Disease ◽

Disease Genes ◽

Protein Protein Interaction ◽

Interaction Partners ◽

And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

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