Small Transcripts Research Articles

Parathyroid hormone (PTH)/PTH-related peptide receptor messenger ribonucleic acids are widely distributed in rat tissues

PTH/PTH-related peptide (PTHrP) receptor mRNAs are widely distributed in rat tissues. PTH and PTHrP, a peptide responsible for hypercalcemia associated with cancers, bind equivalently to common receptors that initially were cloned from rat bone and opossum renal cell cDNA libraries. In this study we used rat PTH/PTHrP receptor cDNA to probe for receptor expression in different rat tissues by Northern blot analysis. PTH/PTHrP receptor transcripts are highly expressed in PTH target tissues, kidney and bone. Receptor transcripts, however, also are expressed in many other tissues, including aorta, adrenal gland, bladder, brain, cerebellum, breast, heart, ileum, liver, lung, skeletal muscle, ovary, placenta, skin, spleen, stomach, uterus, and testes. The major transcript in most tissues is 2.3-2.5 kilobases in size. At least two larger mRNAs are observed in kidney and liver, and smaller transcripts are found in kidney, skin, and testes. The most abundant testicular transcript is 1.4-1.5 kilobases in size, and it hybridizes with two different cDNA probes that encode portions of the receptor sequence from the putative fourth transmembrane domain to its C-terminal end. It does not hybridize, however, with a probe encoding the first 107 residues of the receptor sequence. Although, PTH/PTHrP receptor mRNAs are highly expressed in kidney and bone, classic PTH targets that are associated with calcium homeostasis, their wide tissue distribution suggests that PTH and/or PTHrP have other physiological roles, particularly in these other tissues. The mechanisms leading to tissue-specific expression of PTH/PTHrP receptor transcripts of different sizes and the functions of these mRNAs remain to be determined.

Isolation and characterization of the chicken cystatin-encoding gene: mapping transcription start point and polyadenylation sites

A 6.9-kb fragment containing coding sequences for chicken egg white cystatin (CsnEW) was isolated from a chicken genomic library using the CsnEW cDNA as a probe. The gene is approximately 2.4 kb in length; it contains three exons, two introns and two polyadenylation signals. The exon-intron arrangement corresponds exactly with those of other members of the Csn superfamily. The sequence of the 5' flanking region contains two SP1-binding sites and a high G + C content suggestive of a housekeeping gene. All tissues studied express CsnEW mRNA; Northern analysis showed that CsnEW mRNA levels are most abundant in lung and least abundant in liver and spleen. Mapping of the 3' end of the CsnEW mRNA isolated from brain tissue resolved two CsnEW mRNA species. The larger transcript resulting from the use of the second polyadenylation signal was more abundant than the smaller transcript. Determination of the transcription start point ( tsp) of CsnEW mRNA by primer extension and RNase protection assays showed that CsnEW mRNA from a number of chicken tissues was approximately 40–50 nucleotides shorter than that predicted from the CsnEW cDNA isolated from chicken oviduct.

Complete nucleotide sequence of a linear plasmid from Streptomyces clavuligerus and characterization of its RNA transcripts

The complete nucleotide sequence of a small linear plasmid (pSCL1) from Streptomyces clavuligerus has been determined. This plasmid is 11,696 bp in length, has a 72% G+C content, and has approximately 900-bp inverted terminal repeat sequences. A comparison of the inverted terminal repeats of pSCL1 with those of a linear plasmid from S. rochei shows that the two terminal sequences have a high degree of similarity (approximately 70%). Several small inverted repeats found in the long terminal sequences of both plasmids are also conserved. An analysis of the sequence and codon preferences indicates that pSCL1 has seven or eight highly probable protein-coding open reading frames (ORFs). However, only two RNA species encoded by pSCL1 were detected in S. clavuligerus grown in liquid culture. The larger of these transcripts (900 nucleotides) corresponds to an ORF and is likely to be an mRNA for a protein similar to the KorA protein of pIJ101. The smaller transcript (460 nucleotides) does not correspond to any ORF; however, its 5' end is complementary to the 5' end of a predicted mRNA, suggesting that it may function as an antisense RNA. The larger of the two RNA species was present at a high level during the early stage of growth in liquid medium, and then its apparent rate of transcription decreased and remained at a lower level through the later stages; the level of the smaller RNA species remained relatively constant through all stages of growth.

An Arabidopsis thaliana Gene with Sequence Similarity to the S-Locus Receptor Kinase of Brassica oleracea : Sequence and Expression

Primary signal transduction plays a vital role in the way plants react to environmental and developmental signals. We report the sequence and expression of a putative receptor kinase gene, ARK1, in Arabidopsis thaliana that may be important in this regard. This Arabidopsis gene encodes a transmembrane protein with a cytoplasmic kinase catalytic domain, a transmembrane region, and an extracellular domain with sequence similarity to the secreted S-locus glycoprotein (SLG) gene of Brassica oleracea. This structure is similar to the S-locus receptor kinase (SRK) gene of Brassica and to the receptor kinase ZmPK1 gene of maize. RNA blots indicate that transcripts accumulate predominantly in leaf tissue, with limited amounts in stem and floral bud tissue and no detectable transcripts accumulating in root tissue. A smaller transcript that could be an alternative transcript of ARK1 also accumulates in leaf tissue. This transcript possibly encodes a secreted SLG-like glycoprotein that lacks transmembrane and kinase domains. The predominantly vegetative expression of ARK1 indicates that this gene is not primarily involved in pollen/pistil interactions in Arabidopsis.

Molecular cloning and sequence analysis of cdc27+ required for the G2-M transition in the fission yeast Schizosaccharomyces pombe.

The cell division cycle gene cdc27+ of the fission yeast Schizosaccharomyces pombe is required for the transition from G2 into mitosis. Genetic and physiological experiments suggest a close relationship between cdc27+ and the cdc2+ gene, a key regulator of mitosis in yeast and also in higher eukaryotic cells. We isolated the cdc27+ gene by complementation of a temperature-sensitive cdc27 mutant. The DNA sequence of this gene predicts a 1116 nucleotide open reading frame split by five short introns, ranging in size from 49 to 74 nucleotides. Analysis of cDNA clones confirmed the structure of the gene. The deduced cdc27+ gene product consists of 372 amino acids with a predicted Mr of 43 kDa. No homology of the predicted protein with known proteins could be found, thus the cdc27+ gene encodes a novel function required for the G2-M transition. Northern analysis revealed two mRNAs of 1.4 and 2.2 kb transcribed from this gene, the smaller transcript being approximately tenfold more abundant than the larger. The level of cdc27+ mRNAs remained constant through the cell cycle indicating that the time of action of the cdc27+ gene, which is known to be regulated by elements of the mitotic control, is not determined by periodic accumulation of its transcripts.

Structure of DRE, a retrotransposable element which integrates with position specificity upstream of Dictyostelium discoideum tRNA genes.

Different Dictyostelium discoideum strains contain between 2 and 200 copies of a retrotransposable element termed DRE (Dictyostelium repetitive element). From the analysis of more than 50 elements, it can be concluded that DRE elements always occur 50 +/- 3 nucleotides upstream of tRNA genes. All analyzed clones contain DRE in a constant orientation relative to the tRNA gene, implying orientation specificity as well as position specificity. DRE contains two open reading frames which are flanked by nonidentical terminal repeats. Long terminal repeats (LTRs) are composed of three distinct modules, called A, B, and C. The tRNA gene-proximal LTR is characterized by one or multiple A modules followed by a single B module (AnB). With respect to the distal LTR, two different subforms of DRE have been isolated. The majority of isolated clones contains a distal LTR composed of a B module followed by a C module (BC), whereas the distal LTR of the other subform contains a consecutive array of a B module, a C module, a slightly altered A module, another B module, and another C module (BC.ABC). Full-length as well as smaller transcripts from DRE elements have been detected, but in comparison with the high copy number in D. discoideum strains derived from the wild-type strain NC4, transcription is rather poor.

Structure of DRE, a retrotransposable element which integrates with position specificity upstream of Dictyostelium discoideum tRNA genes.

Different Dictyostelium discoideum strains contain between 2 and 200 copies of a retrotransposable element termed DRE (Dictyostelium repetitive element). From the analysis of more than 50 elements, it can be concluded that DRE elements always occur 50 +/- 3 nucleotides upstream of tRNA genes. All analyzed clones contain DRE in a constant orientation relative to the tRNA gene, implying orientation specificity as well as position specificity. DRE contains two open reading frames which are flanked by nonidentical terminal repeats. Long terminal repeats (LTRs) are composed of three distinct modules, called A, B, and C. The tRNA gene-proximal LTR is characterized by one or multiple A modules followed by a single B module (AnB). With respect to the distal LTR, two different subforms of DRE have been isolated. The majority of isolated clones contains a distal LTR composed of a B module followed by a C module (BC), whereas the distal LTR of the other subform contains a consecutive array of a B module, a C module, a slightly altered A module, another B module, and another C module (BC.ABC). Full-length as well as smaller transcripts from DRE elements have been detected, but in comparison with the high copy number in D. discoideum strains derived from the wild-type strain NC4, transcription is rather poor.

Molecular analysis of the Neurospora clock: cloning and characterization of the frequency and period-4 genes.

Genetic analysis of Neurospora crassa has identified many mutants that affect the biological clock. In this article we review the cloning of two of these genes, frq and prd-4. Both genes were isolated using a chromosome walk technique. Subcloning experiments and subsequent Northern analysis of frq implicate the importance of two transcripts that emanate from this locus. In preliminary data, no protein-coding region is evident in the smaller transcript; the larger transcript contains a 962-amino acid open reading frame. The open reading frame shows limited homology to per, a clock gene identified in Drosophila. Sequence analysis of all existing frq alleles suggests that the defect in each case lies within the open reading frame. Successful cloning of the prd-4 gene required walking a distance of greater than 40 kb. A physical map of this region has been constructed using restriction analysis. The dominance-recessive relationship of prd-4 and prd-4+ was established by examining the period lengths of strains harboring a wide range of prd-4/prd-4+ nuclear ratios.

Prolactin receptor gene expression in the rabbit: Identification, characterization and tissue distribution of several prolactin receptor messenger RNAs encoding a unique precursor

The expression of the prolactin (PRL) receptor gene was studied in rabbit tissues by Northern blot and S1 mapping analysis of mRNA preparations. Rabbit mammary gland contained three major (10.5, 3.4, and 2.7 kb) and one minor (6.2 kb) prolactin receptor poly(A) + RNA transcripts all of which contain the entire coding sequence of the long form of PRL receptor. Each of these mammary mRNAs hybridized equally well with cDNA sequences encoding either the NH 2 terminal, middle, or COOH terminal part of the rabbit mammary PRL receptor. The four mRNAs differed only in their 5'- and 3'-untranslated regions. The 10.5 kb mammary transcript was further shown to represent a primary transcript of nuclear origin. Among the various rabbit tissues tested, male and female adrenals, mammary gland, ovaries, and jejunum contained the highest level of prolactin receptor mRNA. The prolactin receptor gene was also expressed at moderate to weak abundance in uterus, liver, kidney, pancreas, testis and seminal vesicles. No prolactin receptor mRNA species were detected in adult muscle, lung, total brain, placental cotyledons and spleen, and in thymus from young animals. In all the rabbit tissues examined, the same four PRL receptor poly(A) + RNA transcripts identified in the mammary gland were expressed and no additional transcript(s) were detected. Variations in the relative proportion of the 10.5 kb transcript and the two smaller transcripts were observed, while the ratio of the 3.4 and 2.7 kb mRNAs remained unchanged. These findings ask for the role of these different transcripts generated in the rabbit, all of which encode the same long form of PRL receptor precursor but have heterogenous 5'- and 3'-untranslated regions. Moreover, they suggest that the various forms of PRL receptor mRNA originate through differential splicing of a single PRL receptor gene.

Alternative mRNAs encoding the alpha 1b-adrenergic receptor are expressed in a tissue-dependent manner in the Sprague-Dawley rat.

Probing total cellular and poly [A+] RNA isolated from various rat tissues with a full-length cDNA encoding the hamster alpha 1-adrenergic receptor results in detection of two transcripts, 3.3 kb and 2.7 kb, which probably both encode the alpha 1b-adrenergic receptor subtype. Both the 3.3 kb and 2.7 kb mRNAs were found to be associated with hepatic polysomes which suggests that these mRNA species are translated into protein. Using non-overlapping 5' and 3' cDNA probes, large sequence differences were not evident between the 3.3 kb and 2.7 kb mRNAs, although the 3'-probe hybridized to a 4.0 kb mRNA in addition to the two smaller transcripts in poly [A+] RNA isolated from renal cortex, but not other tissues. The relative amounts of the 3.3 kb and 2.7 kb mRNAs varied considerably among the five tissues studied. However, the ratio of the two transcripts remained relatively constant in the same tissue taken from animals at different developmental ages. Currently, the physiological significance of multiple alpha 1b-adrenergic receptor gene transcripts is unclear. However, our results suggest that alpha 1b-adrenergic receptor gene expression in the rat is under complex regulatory control that in part is tissue-dependent.

CDNA cloning of the B cell membrane protein CD22: a mediator of B-B cell interactions.

We have cloned a full-length cDNA for the B cell membrane protein CD22, which is referred to as B lymphocyte cell adhesion molecule (BL-CAM). Using subtractive hybridization techniques, several B lymphocyte-specific cDNAs were isolated. Northern blot analysis with one of the clones, clone 66, revealed expression in normal activated B cells and a variety of B cell lines, but not in normal activated T cells, T cell lines, Hela cells, or several tissues, including brain and placenta. One major transcript of approximately 3.3 kb was found in B cells although several smaller transcripts were also present in low amounts (approximately 2.6, 2.3, and 1.6 kb). Sequence analysis of a full-length cDNA clone revealed an open reading frame of 2,541 bases coding for a predicted protein of 847 amino acids with a molecular mass of 95 kD. The BL-CAM cDNA is nearly identical to a recently isolated cDNA clone for CD22, with the exception of an additional 531 bases in the coding region of BL-CAM. BL-CAM has a predicted transmembrane spanning region and a 140-amino acid intracytoplasmic domain. Search of the National Biological Research Foundation protein database revealed that this protein is a member of the immunoglobulin super family and that it had significant homology with three homotypic cell adhesion proteins: carcinoembryonic antigen (29% identity over 460 amino acids), myelin-associated glycoprotein (27% identity over 425 amino acids), and neural cell adhesion molecule (21.5% over 274 amino acids). Northern blot analysis revealed low-level BL-CAM mRNA expression in unactivated tonsillar B cells, which was rapidly increased after B cell activation with Staphylococcus aureus Cowan strain 1 and phorbol myristate acetate, but not by various cytokines, including interleukin 4 (IL-4), IL-6, and gamma interferon. In situ hybridization with an antisense BL-CAM RNA probe revealed expression in B cell-rich areas in tonsil and lymph node, although the most striking hybridization was in the germinal centers. COS cells transfected with a BL-CAM expression vector were immunofluorescently stained positively with two different CD22 antibodies, each of which recognizes a different epitope. Additionally, both normal tonsil B cells and a B cell line were found to adhere to COS transfected with BL-CAM in the sense but not the antisense direction.(ABSTRACT TRUNCATED AT 400 WORDS)

A human Hox 1 homeobox gene exhibits myeloid-specific expression of alternative transcripts in human hematopoietic cells

As part of a survey of the expression of homeobox-containing genes in human hematopoietic cells, we identified a novel gene (PL1) expressed only in cells of the myelomonocytic lineage (Shen et al., Proc. Natl. Acad. Sci, USA 86, 8536, 1989). On Northern gel analysis, major transcripts of 3.0 and 2.2 kb length are observed. Alternatively spliced homeobox-containing cDNAs, corresponding to the major transcripts, have been cloned from two myeloid leukemia cell libraries. The two cDNAs share the homeodomain and 3' flanking region but have unique 5' flanking regions. The longer transcript, would encode a 496 amino acid homeobox-containing protein, while the shorter message would encode a 94 amino acid homeobox-containing protein lacking the extended amino-terminal region. These two transcripts are differentially expressed in human leukemia cell lines. The larger transcript is exclusively expressed in cells with myelomonocytic features, while the smaller transcript is expressed in a variety of hematopoietic cell types. PL mRNA is also detectable in normal human bone marrow by RNAse protection. Neither transcript is expressed in uninduced teratocarcinoma cells or in the adult human tissues surveyed. The homeodomain is identical to the genomic sequence for Hox 1H, a newly identified member of the Hox 1 locus (Acampora et al. Nucl. Acids Res. 17, 10385, 1989). The PL1 gene was localized to chromosome 7 using chromosome specific blots and sublocalized to region pI4-21 by in situ hybridization of chromosomal spreads, confirming its location within the Hox 1 complex.

Pattern of transcription of the genome of equine infectious anemia virus

The pattern of expression of the equine infectious anemia virus (EIAV) genome in a persistently infected canine cell line was determined. Five EIAV-specific transcripts (8.2, 5.0, 4.0, 2, and 1.8 kilobases [kb]) were detected by using subgenomic restriction enzyme fragments of EIAV DNA and EIAV-specific oligonucleotides as probes. The 8.2-kb mRNA could be shown to represent viral genomic RNA, whereas the smaller transcripts were generated by splicing events. Evidence was obtained that indicated that each subgenomic RNA species shared a common 5'-splice donor. The 5.0-kb mRNA was found to be expressed at relatively low levels, was difficult to detect consistently, and appeared to be generated by a single splicing event which linked the 5' exon to the 3' region of pol. The 4.0-kb transcript was concluded to be the env mRNA on the basis of its hybridization pattern with the various probes and its abundance. The 2-kb species was found to be multiply spliced and was encoded by sequences derived from orf2 but was not detected by probes representing 3'-env/3'-orf sequences. The 1.8-kb species was shown to consist of sequences representing orf1, part of orf2, and the 3'-orf/env and may represent the message for the EIAV trans-activator gene.

A Second Thyroglobulin Messenger RNA Species (rTg-2) in Rat Thyrocytes

A 0.95-kilobase (kb) thyrocyte RNA, initially detected in our 1B-6 subclone of Fisher rat thyrocytes (FRTL-5) using an oligonucleotide probe complementary to the 5' end of rat thyroglobulin (Tg) mRNA, was also detected in cultured thyrocytes of the Wistar rat (WRT cells) and in freshly isolated normal rat thyroid tissue. This transcript was thyroid specific and as abundant as the previously characterized 9.0-kb Tg mRNA in the cultured thyroid cells under the growth conditions employed. The smaller RNA (designated rTg-2 mRNA) was cytoplasmic, polyadenylated, and regulated by TSH. Preliminary characterization with several oligonucleotide probes showed that rTg-2 shared coding information present at the 5', but not the 3', end of the 9.0-kb Tg mRNA. Sequencing of the cloned rTg-2 cDNA showed that it was homologous to human and other higher vertebrate Tg cDNAs at its 5' coding end, but contained additional nonhomologous coding and noncoding sequences at the 3' end. The junction between the shared and unique sequences in rTg-2 mRNA occurred at the exon-5/intron-5 boundary in the Tg gene. This smaller transcript has not previously been reported and encodes elements known to be of structural and functional significance in the 330-kD Tg monomer. A putative polypeptide product from rTg-2 mRNA may play an important role in thyroid function and thyroid autoimmunity.

Expression of the α and β Retinoic Acid Receptors in Skin

Retinoic acid receptor (RAR) -alpha and -beta transcripts are expressed in rat and human skin, and in rat and human dermal fibroblasts and keratinocytes in vitro. RAR-alpha transcripts (ca. 2.8 and 3.6 kb) were expressed in all tissues but were more abundant in dermis and dermal fibroblasts than in epidermis or keratinocytes. RAR-beta mRNA was expressed in skin, but patterns of expression differed between human and neonatal rat samples. In human dermal fibroblasts, keratinocytes and whole skin, two RAR-beta transcripts (ca. 3.1 and 3.4 kb) were expressed. Conversely, in neonatal rat skin, dermal fibroblasts, and keratinocytes only the smaller transcript was detectable and was more abundant in cultured cells than in whole tissue. These results suggest that retinoic acid may have complex, as yet undefined, RAR-mediated regulatory functions in both dermis and epidermis.

An antisense mRNA directs the covalent modification of the transcript encoding fibroblast growth factor in Xenopus oocytes

The Xenopus oocyte contains three maternal basic fibroblast growth factor (bFGF) transcripts, the largest of which encodes the complete bFGF polypeptide. We show that the smallest transcript is transcribed in the opposite direction of the largest transcript and overlaps part of the coding sequence of bFGF. This antisense transcript encodes a highly conserved 25 kd polypeptide. In addition, the antisense transcript causes modification of the mRNA encoding bFGF during maturation of the oocyte, converting half of the adenine residues to inosine in the region of overlap between the sense and antisense transcripts. As this activity acts only on double-stranded RNA, the two mRNAs must be hybridized in the oocyte. We discuss a possible role for the antisense transcript in regulating the stability of the bFGF mRNA.

Structural analysis of the uEGF gene in the sea urchinStrongylocentrotus purpuratus reveals more similarity to vertebrate than to invertebrate genes with EGF-like repeats

The gene uEGF, a member of the epidermal growth factor family in the sea urchin Stronglyocentrotus purpuratus, is known to express two transcripts that are regulated developmentally in the embryo. We have partially sequenced several uEGF genomic and cDNA clones. We suggest that the smaller transcript is the result of splicing out an internal region present in the larger mRNA, probably with eight EGF-like repeats. The predicted two uEGF products have a signal peptide followed by an EGF-like repeat and a region with approximately 120 amino acids homologous to domain III in complement component C1s. Following these domains, the short product has 12 tandem EGF-like repeats, whereas the long product has approximately 20 tandem repeats. At the carboxy terminus both products have a region homologous to avidin. Unlike Notch and lin-12, no transmembrane domain was found in uEGF. We also show here that uEGF shares two characteristics with vertebrate members of the EGF family, but not with invertebrate members of the same family. (1) All the EGF-like domains sequenced are represented by single exons. (2) All the introns sequenced follow the first nucleotide of a codon. This supports the hypothesis that the organization of the EGF-like domains in vertebrates and in uEGF derived from a common ancestor. Thus, an alternative molecular datum is provided to support the hypothesis of echinoderm-chordate relationships.

Identification and tissue distribution of messenger RNA for the growth hormone receptor in the rabbit

Rabbit liver, a rich source of specific growth hormone (GH) receptors, contains three mRNA transcripts (4.2-4.5 kb, 3.1-3.2 kb, and 1.8-2.0 kb) which hybridize strongly to oligonucleotide probes complementary to nucleotide sequences in the extracellular and cytoplasmic regions of the rabbit liver GH receptor. The approximately 4.5 kb transcript was the most abundant and showed some sex difference (male greater than female) and a significant, approximately 2 fold increase in late pregnancy - observations consistent with changes seen in the specific 125I-hGH binding capacity of rabbit liver membranes prepared from the same tissue samples. The approximately 4.5 kb mRNA species, but not the smaller transcripts, was also detected, at lower abundance, in rabbit kidney, heart and lung but not in mammary gland, which is known to lack 125I-GH binding activity. These studies have identified the nature of the mRNA transcripts coding for the GH receptor in recognized/potential GH target tissues in the rabbit. The regulation of the major GH receptor mRNA in rabbit liver appears to broadly reflect known changes in expressed receptor protein.

An unusual split Drosophila heat shock gene expressed during embryogenesis, pupation and in testis

Gene 2, one of the seven heat shock genes from locus 67B of Drosophila melanogaster, is transcribed into two polyadenylated RNAs having different developmental profiles of expression. The smaller transcript, of about 560 nucleotides, is expressed from mid-embryogenesis to the first two larval stages and again at the beginning of pupation. The larger transcript, 780 nucleotides, contains an additional 5′ exon, accounting for its larger size. It is detected in pupae and adults, is male-specific and is localized in the testes. Heat shock does not affect the abundance of these two transcripts but induces the accumulation of a third RNA species of about 2000 nucleotides. This heat-shock RNA has the same cap site as the embryonic transcript, while its 3′ portion entirely includes the neighbouring hsp22 gene. It appears, therefore, that in this case, heat shock alters the normal transcription termination process. By contrast to most heat shock genes, gene 2 contains several micro introns. One long open reading frame common to the three transcripts encodes a putative polypeptide of 111 amino acid residues. No homology was found with the other small heat shock genes of locus 67B.

Expression of Somatomedin/Insulin-Like Growth Factor Messenger Ribonucleic Acids in the Human Fetus: Identification, Characterization, and Tissue Distribution*

Several lines of evidence indicate that multiple human fetal tissues synthesize somatomedins/insulin-like growth factors (Sm/IGFs). To investigate the synthesis of Sm/IGFs in vivo, we isolated polyadenylated RNAs from multiple human fetal tissues of 16-20 weeks gestation and performed Northern and dot-blot analyses using 32P-labeled cDNAs and oligodeoxyribonucleotide (oligomer) probes complementary to human Sm-C/IGF-I and IGF-II mRNAs. Sm-C/IGF-I mRNAs were present in all tissues studied. IGF-II mRNAs were detectable in all tissues except the cerebral cortex and hypothalamus. IGF-II mRNA levels were consistently higher than Sm-C/IGF-I mRNAs in all tissues where IGF-II mRNAs were detectable (varying from 2-fold higher in spleen and thymus to 650-fold higher in liver), suggesting that IGF-II is synthesized in greater quantities than Sm-C/IGF-I in most tissues during early fetal life. Liver, adrenal, and skeletal muscle had the highest levels of IGF-II mRNAs, while placenta and stomach had the highest level of Sm-C/IGF-I mRNAs. Multiple Sm-C/IGF-I and IGF-II transcripts were identified with estimated sizes 0.7, 5.3, and 8.0 kilobases (kb) for Sm-C/IGF-I and 1.8, 2.0, 2.8, 3.0, 4.0, 4.8, and 6.2 kb for IGF-II. The 5.3-kb species was the most abundant Sm-C/IGF-I mRNA. The largest Sm-C/IGF-I transcript (8.0 kb) was identified in the intestine, muscle, kidney, placenta, stomach, heart, skin, pancreas, hypothalamus, and brain stem and was most abundant in the hypothalamus and muscle. The smallest transcript (0.7 kb) was detectable only in spleen, adrenal, placenta, and stomach. On the other hand, nearly all species of IGF-II mRNAs were found in tissues with detectable mRNAs, with the 6.2-kb mRNA being the most abundant. The variation in abundance and species of Sm-C/IGF-I and IGF-II mRNAs among different human fetal tissues suggests tissue-specific differences in Sm-C/IGF-I and IGF-II gene expression, mRNA precursor processing, and/or mRNA stability. Such differences may have significance for the roles of Sm-C/IGF-I and IGF-II during human fetal development. The finding of Sm/IGF mRNAs in many human fetal tissues also supports a local role for Sm/IGFs in human fetal development.